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154 results on '"Ferid, Haddad"'

1. Ultrahigh-Dose-Rate Proton Irradiation Elicits Reduced Toxicity in Zebrafish Embryos

Author

Gaëlle Saade, Eva Bogaerts, Sophie Chiavassa, PhD, Guillaume Blain, Grégory Delpon, PhD, Manon Evin, Youssef Ghannam, Ferid Haddad, PhD, Karin Haustermans, MD, PhD, Charbel Koumeir, PhD, Ellina Macaeva, PhD, Lydia Maigne, PhD, Quentin Mouchard, PhD, Noël Servagent, PhD, Edmond Sterpin, PhD, Stéphane Supiot, MD, PhD, and Vincent Potiron, PhD

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Purpose: Recently, ultrahigh-dose-rate radiation therapy (UHDR-RT) has emerged as a promising strategy to increase the benefit/risk ratio of external RT. Extensive work is on the way to characterize the physical and biological parameters that control the so-called “Flash” effect. However, this healthy/tumor differential effect is observable in in vivo models, which thereby drastically limits the amount of work that is achievable in a timely manner. Methods and Materials: In this study, zebrafish embryos were used to compare the effect of UHDR irradiation (8-9 kGy/s) to conventional RT dose rate (0.2 Gy/s) with a 68 MeV proton beam. Viability, body length, spine curvature, and pericardial edema were measured 4 days postirradiation. Results: We show that body length is significantly greater after UHDR-RT compared with conventional RT by 180 µm at 30 Gy and 90 µm at 40 Gy, while pericardial edema is only reduced at 30 Gy. No differences were obtained in terms of survival or spine curvature. Conclusions: Zebrafish embryo length appears as a robust endpoint, and we anticipate that this model will substantially fasten the study of UHDR proton-beam parameters necessary for “Flash.”

Published
2023
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2. Therapeutic efficacy of 166Holmium siloxane in microbrachytherapy of induced glioblastoma in minipig tumor model

Author

Mehrdad Khoshnevis, Richard Brown, Sara Belluco, Ilyes Zahi, Luca Maciocco, Catherine Bonnefont-Rebeix, Elodie Pillet-Michelland, Jonathan Tranel, Thierry Roger, Christophe Nennig, Patrick Oudoire, Lionel Marcon, Olivier Tillement, Cédric Louis, Hélène Gehan, Manuel Bardiès, Maurizio Mariani, Valeria Muzio, Jean-Philippe Meunier, Charlotte Duchemin, Nathalie Michel, Estelle N’Tsiba, Ferid Haddad, Thierry Buronfosse, Claude Carozzo, and Frédérique Ponce

Subjects
glioblastoma, U87 cells, minipig, 166Ho, microbrachytherapy, animal model, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Glioblastoma is considered the most common malignant primary tumor of central nervous system. In spite of the current standard and multimodal treatment, the prognosis of glioblastoma is poor. For this reason, new therapeutic approaches need to be developed to improve the survival time of the glioblastoma patient. In this study, we performed a preclinical experiment to evaluate therapeutic efficacy of 166Ho microparticle suspension administered by microbrachytherapy on a minipig glioblastoma model. Twelve minipigs were divided in 3 groups. Minipigs had injections into the tumor, containing microparticle suspensions of either 166Ho (group 1; n = 6) or 165Ho (group 2; n = 3) and control group (group 3; n = 3). The survival time from treatment to euthanasia was 66 days with a good state of health of all minipigs in group 1. The median survival time from treatment to tumor related death were 8.6 and 7.3 days in groups 2 and control, respectively. Statistically, the prolonged life of group 1 was significantly different from the two other groups (p < 0.01), and no significant difference was observed between group 2 and control (p=0.09). Our trial on the therapeutic effect of the 166Ho microparticle demonstrated an excellent efficacy in tumor control. The histological and immunohistochemical analysis showed that the efficacy was related to a severe 166Ho induced necrosis combined with an immune response due to the presence of the radioactive microparticles inside the tumors. The absence of reflux following the injections confirms the safety of the injection device.

Published
2022
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3. How Efficient Are Monte Carlo Calculations Together With the Q-System to Determine Radioactive Transport Limits? Case Study on Medical Radionuclides

Author

Maddalena Maietta, Ferid Haddad, and Sebastien Avila

Subjects
radioactive transport, radiopharmaceuticals, Monte Carlo, Q-system, container, Medicine (General), R5-920
Abstract

The development of the so-called theranostics approach, in which imaging information are used to define a personalized therapeutic strategy, is driving the increasing use of radionuclides in nuclear medicine. They are artificially produced either in nuclear reactors, charged particle accelerators, or using radionuclide generators. Each method leads to radioisotopes with different characteristics and then clinical utility. In the first two cases they are extracted from stable or radioactive target bombarded with a particle beam. After extraction/purification of the target, the radionuclides, either implanted on solid or in liquid form, needs to be transported to a centralized production site, a radiopharmacy or an hospital. The transport of needed radioactive material must obey strict rules. For a radionuclide, a limit in activity that it is possible to transport has been established for each type of allowed packages. For type A package these limits are called A1 (for special form sources, i.e., certified perfectly sealed and encapsulated sources) and A2 (for non-special form sources). However, these limits can be easily reached if the activity to transport is high or if the radionuclide of interest is a “non–conventional” one. Indeed, for many radionuclides, there are no available/tabulated A1 and A2 and, in these cases, a very conservative set of values is imposed. This is in particular the case for some of the non-conventional radionuclide of interest in medicine (as for example Tb-149 or Tb-161). The non-tabulated values, and in general the A1/A2 limit, can be evaluated following the so-called Q-system and using Monte Carlo calculations. In the present work, we have used the MCNPX Monte Carlo code to evaluate dose rate values in different exposure scenarios. This has allowed us to determine A1/A2 coefficients for several non-conventional radionuclides of interest for medical applications. The developed technique can be extended easily to other radionuclides and can be adapted in case of changes in regulatory rules.

Published
2022
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4. Terbium Medical Radioisotope Production: Laser Resonance Ionization Scheme Development

Author

Vadim Maratovich Gadelshin, Roberto Formento Cavaier, Ferid Haddad, Reinhard Heinke, Thierry Stora, Dominik Studer, Felix Weber, and Klaus Wendt

Subjects
CERN-MEDICIS, RISIKO mass separator, terbium, gadolinium, laser resonance ionization, isotope separation, Medicine (General), R5-920
Abstract

Terbium (Tb) is a promising element for the theranostic approach in nuclear medicine. The new CERN-MEDICIS facility aims for production of its medical radioisotopes to support related R&D projects in biomedicine. The use of laser resonance ionization is essential to provide radioisotopic yields of highest quantity and quality, specifically regarding purity. This paper presents the results of preparation and characterization of a suitable two-step laser resonance ionization process for Tb. By resonance excitation via an auto-ionizing level, the high ionization efficiency of 53% was achieved. To simulate realistic production conditions for Tb radioisotopes, the influence of a surplus of Gd atoms, which is a typical target material for Tb generation, was considered, showing the necessity of radiochemical purification procedures before mass separation. Nevertheless, a 10-fold enhancement of the Tb ion beam using laser resonance ionization was observed even with Gd:Tb atomic ratio of 100:1.

Published
2021
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5. Is 70Zn(d,x)67Cu the Best Way to Produce 67Cu for Medical Applications?

Author

Etienne Nigron, Arnaud Guertin, Ferid Haddad, and Thomas Sounalet

Subjects
67Cu, production, theranostic, cross section, deuteron reactions, accelerators, Medicine (General), R5-920
Abstract

The pair of copper radionuclides 64Cu/67Cu (T1/2 = 12. 7 h/61.8 h) allows, respectively, PET imaging and targeted beta therapy. An analysis of the different production routes of 67Cu with charged particles was performed and the reaction 70Zn(d,x) route was identified as a promising one. It may allow the production of 67Cu without 64Cu. The production cross section has been measured up to 28.7 MeV. Measurements were done using the well-known stacked-foils technique using 97.5% enriched 70Zn homemade electroplated targets. These measurements complement at higher incident energies the only set of data available in nuclear databases. The results show that using a 26 MeV deuteron beam and a highly enriched 70Zn target, it is possible to produce high purity 67Cu comparable to that obtained using photoproduction. This production route can be of interest for future linear accelerators under development where mA deuteron beams can be available if adequate targetry is developed.

Published
2021
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6. CERN-MEDICIS: A Review Since Commissioning in 2017

Author

Charlotte Duchemin, Joao P. Ramos, Thierry Stora, Essraa Ahmed, Elodie Aubert, Nadia Audouin, Ermanno Barbero, Vincent Barozier, Ana-Paula Bernardes, Philippe Bertreix, Aurore Boscher, Frank Bruchertseifer, Richard Catherall, Eric Chevallay, Pinelopi Christodoulou, Katerina Chrysalidis, Thomas E. Cocolios, Jeremie Comte, Bernard Crepieux, Matthieu Deschamps, Kristof Dockx, Alexandre Dorsival, Valentin N. Fedosseev, Pascal Fernier, Robert Formento-Cavaier, Safouane El Idrissi, Peter Ivanov, Vadim M. Gadelshin, Simone Gilardoni, Jean-Louis Grenard, Ferid Haddad, Reinhard Heinke, Benjamin Juif, Umair Khalid, Moazam Khan, Ulli Köster, Laura Lambert, G. Lilli, Giacomo Lunghi, Bruce A. Marsh, Yisel Martinez Palenzuela, Renata Martins, Stefano Marzari, Nabil Menaa, Nathalie Michel, Maxime Munos, Fabio Pozzi, Francesco Riccardi, Julien Riegert, Nicolas Riggaz, Jean-Yves Rinchet, Sebastian Rothe, Ben Russell, Christelle Saury, Thomas Schneider, Simon Stegemann, Zeynep Talip, Christian Theis, Julien Thiboud, Nicholas P. van der Meulen, Miranda van Stenis, Heinz Vincke, Joachim Vollaire, Nhat-Tan Vuong, Benjamin Webster, Klaus Wendt, Shane G. Wilkins, and the CERN-MEDICIS collaboration

Subjects
CERN, MEDICIS, medical, radionuclides, mass separation, Medicine (General), R5-920
Abstract

The CERN-MEDICIS (MEDical Isotopes Collected from ISolde) facility has delivered its first radioactive ion beam at CERN (Switzerland) in December 2017 to support the research and development in nuclear medicine using non-conventional radionuclides. Since then, fourteen institutes, including CERN, have joined the collaboration to drive the scientific program of this unique installation and evaluate the needs of the community to improve the research in imaging, diagnostics, radiation therapy and personalized medicine. The facility has been built as an extension of the ISOLDE (Isotope Separator On Line DEvice) facility at CERN. Handling of open radioisotope sources is made possible thanks to its Radiological Controlled Area and laboratory. Targets are being irradiated by the 1.4 GeV proton beam delivered by the CERN Proton Synchrotron Booster (PSB) on a station placed between the High Resolution Separator (HRS) ISOLDE target station and its beam dump. Irradiated target materials are also received from external institutes to undergo mass separation at CERN-MEDICIS. All targets are handled via a remote handling system and exploited on a dedicated isotope separator beamline. To allow for the release and collection of a specific radionuclide of medical interest, each target is heated to temperatures of up to 2,300°C. The created ions are extracted and accelerated to an energy up to 60 kV, and the beam steered through an off-line sector field magnet mass separator. This is followed by the extraction of the radionuclide of interest through mass separation and its subsequent implantation into a collection foil. In addition, the MELISSA (MEDICIS Laser Ion Source Setup At CERN) laser laboratory, in service since April 2019, helps to increase the separation efficiency and the selectivity. After collection, the implanted radionuclides are dispatched to the biomedical research centers, participating in the CERN-MEDICIS collaboration, for Research & Development in imaging or treatment. Since its commissioning, the CERN-MEDICIS facility has provided its partner institutes with non-conventional medical radionuclides such as Tb-149, Tb-152, Tb-155, Sm-153, Tm-165, Tm-167, Er-169, Yb-175, and Ac-225 with a high specific activity. This article provides a review of the achievements and milestones of CERN-MEDICIS since it has produced its first radioactive isotope in December 2017, with a special focus on its most recent operation in 2020.

Published
2021
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7. Nuclear data for light charged particle induced production of emerging medical radionuclides

Author

Gaia Pupillo, Liliana Mou, Simone Manenti, Flavia Groppi, Juan Esposito, and Ferid Haddad

Subjects
Physical and Theoretical Chemistry
Abstract

Whatever the radionuclide to be used in nuclear medicine, it is essential to know the expected yield during the production process, but also of all the possible radionuclidic impurities coproduced, that can have an impact on the product final quality, as well as in the related waste management. The availability of the majority of emerging radioisotopes, including the theranostic ones or pairs, is mainly limited by the fact that, for most of them, the optimal production route still needs to be strengthened if not defined in some cases. The aim of this work is to present a review on the charged particle induced nuclear cross sections to produce some emerging radionuclides for medical applications to show that all types of projectiles should be considered in the quest of producing medical radionuclides. An accurate analysis of the production routes is presented for some radionuclides (67Cu, 47Sc, 89Zr, 103Pd, 186gRe, 97Ru, 211At) chosen as examples to highlight (i) how the quality of the final product strongly depends on the chosen target/projectile/energy parameters set, (ii) how deuteron production routes may sometimes be more effective than the proton ones or lead to a different impurity profile and (iii) how α-particle beams may allow to bypass the limitations occurring when using Z = 1 beams. An overview of possible advantages and drawbacks of the cited production routes and of potential cross sections that still need to be measured, is also reported.

Published
2022
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8. Étonnants infinis

Author

Maud Baylac, Jean-Luc Biarrotte, Julien Billard, Dominique Boutigny, Chiara Caprini, Gabriel Chardin, Patrick Chardon, Pierre Cladé, Sabine Crépé-Renaudin, Hélène Courtois, Sylvain David, Sacha Davidson, Emmanuel Dartois, Mirella Del Nero, Jean Duprat, Josquin Errard, Fanny Farget, Berrie Giebels, Vladimir Vava Gligorov, Raphaël Granier De Cassagnac, Saida Guellati, Francesca Gulminelli, Ferid Haddad, Sébastien Incerti, Marc Knecht, Antoine Lemasson, Marianne Lemoine-Goumard, Anne Le Pennec, Araceli Lopez-Martens, Benoit Lott, Pierre-Etienne Macchi, Frédérique Marion, Jacques Marteau, Silvia Niccolai, Mathieu Perrin-Terrin, Guillaume Pignol, Vincent Poireau, Daniel Pomarède, Vivian Poulin, Laurent Serin, Justine Serrano, Yves Sirois, Olivier Sorlin, David Rousseau, Vincent Tatischeff, Teixeira, Ana M., Laurent Vacavant, Véronique Van Elewyck, Marco Zito, Fabian Zomer, Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Annecy de Physique des Particules (LAPP), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), European Organization for Nuclear Research (CERN), AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Laboratoire Kastler Brossel (LKB (Jussieu)), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Univers et Particules de Montpellier (LUPM), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Grand Accélérateur National d'Ions Lourds (GANIL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE (UMR_7585)), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Physique des Deux Infinis Bordeaux (LP2I - Bordeaux), Université de Bordeaux (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Calcul de l'IN2P3 (CC-IN2P3), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Physique des Particules de Marseille (CPPM), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, APC - Cosmologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, and Ursula Bassler

Subjects
[PHYS]Physics [physics], [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph]
Abstract

International audience; L’immensité de notre Univers ne cesse d’intriguer et de stimuler les imaginations.Pour mieux appréhender l’infiniment grand et l’histoire de l’Univers depuis ses tout premiers instants, il faut se tourner vers un autre infini, l’infiniment petit, et ses quarks, leptons et bosons, à la base du modèle standard de la physique des particules. En les étudiant, on cherche à percer le secret de l’organisation de la matière à la plus petite échelle. Sans l’infiniment petit, on ne peut décrire ni le Big Bang, ni le comportement des grandes structures stellaires, ni la naissance de la matière. Et sans ces deux infinis ensemble, on ne peut bâtir les modèles théoriques expliquant la matière noire, l’énergie noire ou fonder la gravitation quantique.Les physiques des infinis sont des physiques hors normes qui se racontent à grand renfort de superlatifs. Elles nécessitent des installations internationales de très grande envergure, et nous entraînent dans des voyages aux confins de la perception où l’on flirte avec la vitesse de la lumière et jongle avec les limites des propriétés de la matière.En trente courts chapitres abondamment illustrés, cet ouvrage rend compte de ce que l’on sait déjà comme de ce que l’on cherche encore.

Published
2022

9. Excitation functions of deuteron induced nuclear reactions on dysprosium targets for the production of the theranostic relevant isotopes of terbium

Author

Michele Colucci, Stefano Carminati, Ferid Haddad, Etienne Nigron, Flavia Groppi, and Simone Manenti

Subjects
Fluid Flow and Transfer Processes, General Physics and Astronomy
Abstract

The physical properties of $${}^{149,152,155,161}$$ 149 , 152 , 155 , 161 Tb enable their use in both diagnostic and therapeutic applications in the field of nuclear medicine. For this reason the optimization of the production routes of these radionuclides is of widespread interest in research. In this work, the feasibility of the production of $${}^{155}$$ 155 Tb and $${}^{161}$$ 161 Tb via the nuclear reactions induced by deuterons on dysprosium target with natural isotopic abundances has been discussed. The cross sections of $${}^{nat}$$ nat Dy(d,x) reactions have been studied in the 12.5–32 MeV energetic range with the stacked-foil technique and the corresponding Thick Target Yields have been obtained. The presence of terbium and dysprosium contaminants ($${}^{156,160}$$ 156 , 160 Tb, $${}^{155,157,159}$$ 155 , 157 , 159 Dy) has been evaluated too.

Published
2022
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10. Microdosimetry and radiolytic species production in UHDR proton beam using GATE and Geant4-DNA

Author

Giovanna Rosa Fois, Guillaume Blain, Sophie Chiavassa, Grégory Delpon, Manon Evin, Vincent Fiegel, Mohammad Ghalei, Ferid Haddad, Incerti, S., Charbel Koumeir, Vincent Métivier, Quentin Mouchard, Freddy Poirier, Vincent Potiron, Noël Servagent, Stéphane Supiot, Hoang Ngoc Tran, Johan Vandenborre, Lydia Maigne, Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, GIP ARRONAX [Nantes], Université de Nantes (UN), Laboratoire de Physique des Deux Infinis Bordeaux (LP2I - Bordeaux), Université de Bordeaux (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Centre d'Etudes Nucléaires de Bordeaux Gradignan (CENBG), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Financial support from Inserm Cancer (PCSI FLASHMOD), Giovanni Mettivier, Sébastien Incerti, Jeremy Brown, Susanna Guatelli, Paolo Russo, Antonio Sarno, Daniele Esposito, Gianfranco Paternò, Silvio Pardi, FLASHMOD, ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
UHDR proton beam, Geant4-DNA, GATE, Microdosimetry, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], radiolytic species, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience

Published
2022

11. Ultrahigh-Dose-Rate Proton Irradiation Elicits Reduced Toxicity in Zebrafish Embryos

Author

Gaëlle Saade, Eva Bogaerts, Sophie Chiavassa, Guillaume Blain, Grégory Delpon, Manon Evin, Youssef Ghannam, Ferid Haddad, Karin Haustermans, Charbel Koumeir, Ellina Macaeva, Lydia Maigne, Quentin Mouchard, Noël Servagent, Edmond Sterpin, Stéphane Supiot, Vincent Potiron, Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Department of Oncology [Leuven, Belgium], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, GIP ARRONAX [Nantes], Université de Nantes (UN), University Hospitals Leuven [Leuven], Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), This work was supported by Inserm Cancer, the Ligue Contre le Cancer, IRC Transformed, Institut de Cancérologie de l’Ouest, the Stichting Tegen Kanker (STK) grant ZKD6219, and the Walloon region EPT grant D7.21214.014-P., FLASHMOD, and UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie

Subjects
Oncology, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiology, Nuclear Medicine and imaging, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; PurposeRecently, ultrahigh-dose-rate radiation therapy (UHDR-RT) has emerged as a promising strategy to increase the benefit/risk ratio of external RT. Extensive work is on the way to characterize the physical and biological parameters that control the so-called “Flash” effect. However, this healthy/tumor differential effect is observable in in vivo models, which thereby drastically limits the amount of work that is achievable in a timely manner.Methods and MaterialsIn this study, zebrafish embryos were used to compare the effect of UHDR irradiation (8-9 kGy/s) to conventional RT dose rate (0.2 Gy/s) with a 68 MeV proton beam. Viability, body length, spine curvature, and pericardial edema were measured 4 days postirradiation.ResultsWe show that body length is significantly greater after UHDR-RT compared with conventional RT by 180 µm at 30 Gy and 90 µm at 40 Gy, while pericardial edema is only reduced at 30 Gy. No differences were obtained in terms of survival or spine curvature.ConclusionsZebrafish embryo length appears as a robust endpoint, and we anticipate that this model will substantially fasten the study of UHDR proton-beam parameters necessary for “Flash.”

Published
2022
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12. Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

Author

Piotr Garnuszek, Cyrille Alliot, Sandrine Huclier-Markai, Viktória Forgács, Ferid Haddad, Dezső Szikra, Renata Mikolajczak, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Cyclotron ARRONAX, and GIP

Subjects
Standardization, Computer science, R895-920, chemistry.chemical_element, Review, RM1-950, 010403 inorganic & nuclear chemistry, 01 natural sciences, Medical care, In vivo studies, 030218 nuclear medicine & medical imaging, Analytical Chemistry, 03 medical and health sciences, Medical physics. Medical radiology. Nuclear medicine, 0302 clinical medicine, Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Scandium, [PHYS]Physics [physics], Pharmacology, Accelerator- and nuclear reactor production, Positron emitters, 3. Good health, 0104 chemical sciences, chemistry, Coordination, Quality specifications, Scandium radionuclides, Biochemical engineering, Therapeutics. Pharmacology, Radiolabeling
Abstract

International audience; AbstractIn the frame of “precision medicine”, the scandium radionuclides have recently received considerable interest, providing personalised adjustment of radiation characteristics to optimize the efficiency of medical care or therapeutic benefit for particular groups of patients. Radionuclides of scandium, namely scandium-43 and scandium-44 (43/44Sc) as positron emitters and scandium-47 (47Sc), beta-radiation emitter, seem to fit ideally into the concept of theranostic pair. This paper aims to review the work on scandium isotopes production, coordination chemistry, radiolabeling, preclinical studies and the very first clinical studies. Finally, standardized procedures for scandium-based radiopharmaceuticals have been proposed as a basis to pave the way for elaboration of the Ph.Eur. monographs for perspective scandium radionuclides.

Published
2021
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13. Hydrogen peroxide formation to investigate the radiolytic ROS production mechanism under proton FLASH conditions

Author

Vincent Fiegel, Guillaume Blain, Manon Evin, Quentin Mouchard, Charbel Koumeir, Noël Servagent, Mohammad Ghalei, Giovanna Rosa Fois, Vincent Métivier, Freddy Poirier, Vincent Potiron, Stéphane Supiot, Ferid Haddad, Grégory Delpon, Sophie Chiavassa, Johan Vandenborre, Lydia Maigne, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, GIP ARRONAX [Nantes], Université de Nantes (UN), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Financial support from Inserm Cancer (PCSI FLASHMOD), GdR MI2B, FLASHMOD, ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
FLASHMOD project, Ultra-High Dose Rate, FLASH conditions, [SDV.CAN]Life Sciences [q-bio]/Cancer, ARRONAX cyclotron, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience

Published
2022

14. Proton Irradiations at Ultra-High Dose Rate vs. Conventional Dose Rate: Strong Impact on Hydrogen Peroxide Yield

Author

Guillaume Blain, Johan Vandenborre, Daphnée Villoing, Vincent Fiegel, Giovanna Rosa Fois, Ferid Haddad, Charbel Koumeir, Lydia Maigne, Vincent Métivier, Freddy Poirier, Vincent Potiron, Stéphane Supiot, Noël Servagent, Grégory Delpon, Sophie Chiavassa, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
Radiation, Radiochemistry, Hydroxyl Radical, Biophysics, Water, Radiology, Nuclear Medicine and imaging, Hydrogen Peroxide, Protons, [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; During ultra-high dose rate (UHDR) external radiation therapy, healthy tissues appear to be spared while tumor control remains the same compared to conventional dose rate. However, the understanding of radiochemical and biological mechanisms involved are still to be discussed. This study shows how the hydrogen peroxide (H2O2) production, one of the reactive oxygen species (ROS), could be controlled by early heterogenous radiolysis processes in water during UHDR proton-beam irradiations. Pure water was irradiated in the plateau region (track-segment) with 68 MeV protons under conventional (0.2 Gy/s) and several UHDR conditions (40 Gy/s to 60 kGy/s) at the ARRONAX cyclotron. Production of H2O2 was then monitored using the Ghormley triiodide method. New values of GTS(H2O2) were added in conventional dose rate. A substantial decrease in H2O2 production was observed from 0.2 to 1.5 kGy/s with a more dramatic decrease below 100 Gy/s. At higher dose rate, up to 60 kGy/s, the H2O2 production stayed stable with a mean decrease of 38% ± 4%. This finding, associated to the decrease in the production of hydroxyl radical (•OH) already observed in other studies in similar conditions can be explained by the well-known spur theory in radiation chemistry. Thus, a two-step FLASH-RT mechanism can be envisioned: an early step at the microsecond scale mainly controlled by heterogenous radiolysis, and a second, slower, dominated by O2 depletion and biochemical processes. To validate this hypothesis, more measurements of radiolytic species will soon be performed, including radicals and associated lifetimes.

Published
2022
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15. Production of polonium from bismuth and purification using TBP resin and Sr resin

Author

Cyrille Alliot, Ali Younes, Gilles Montavon, Ferid Haddad, Steffen Happel, M. Mokili, Aude Bombard, Jafar Sunga Ali, A.C. Bonraisin, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Cyclotron ARRONAX, GIP, Université de Nantes (UN), and Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST)

Subjects
Materials science, Health, Toxicology and Mutagenesis, chemistry.chemical_element, 010402 general chemistry, 010403 inorganic & nuclear chemistry, 7. Clean energy, 01 natural sciences, 12. Responsible consumption, Analytical Chemistry, Bismuth, Radiology, Nuclear Medicine and imaging, Irradiation, ComputingMilieux_MISCELLANEOUS, Spectroscopy, Polonium, [PHYS]Physics [physics], Radiochemistry, Public Health, Environmental and Occupational Health, Radioactive waste, Alpha particle, Pollution, 0104 chemical sciences, Nuclear Energy and Engineering, chemistry, Deuterium, Yield (chemistry), [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract

International audience; A method for the production and purification of polonium from an irradiated bismuth target that minimizes processing time, cost, and generation of radioactive wastes, and increases recovery yield, is proposed. Production is done through two approaches: using a 37-MeV alpha particle beam to produce 210Po, and using a deuteron beam of 16-MeV to produce 210Po, 209Po and 208Po. Separation is performed using TBP-resin, and batch studies were performed to optimize conditions. Bismuth is separated with 7 M HCl, and polonium is successfully retained on the TBP resin. Polonium was recovered using 8 M HNO3 with a 99% yield.

Published
2020
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16. Standards for clinical translation

Author

Clemens Decristoforo, Sason Feldkamp Hayashi, Cecile Bordeau, Ferid Haddad, David Viertl, Claire Deville, Clive Naidoo, Kristina Søborg Pedersen, Mikael Jensen, Ulli Köster, João Galamba Correia, Lurdes Gano, Frank Bruchertseifer, Kristof Baete, Renata Mikolajczak, Sean Collins, Susanne Geistlich, Nick van der Meulen, Bernard Ponsard, Michiel Van de Voorde, and Monica Campillos

Subjects
PRISMAP, radionuclides, pharmaceutical, standardization and harmonization
Abstract

Radiopharmaceuticals are considered Medicinal Products, thereby they must be prepared and applied within the regulated area of pharmaceuticals. This includes radionuclides, which have seen extraordinary advancements in research and development over the last decade in regards to theranostics. The governing EU directives and regulations, including regulatory guidance, cannot keep pace with this development. PRISMAP, the European Medical Radionuclide Program, brings together key nuclear research centres and leading clinical translational research facilities across Europe to provide a sustainable source of high purity grade new radionuclides for the starting research community. One of PRISMAP`s paramount aims is to standardise and harmonise research and development activities with novel radionuclides to cope with pharmaceutical regulatory requirements and provide guidance for clinical translation. The PRISMAP workshop: “Radionuclide Production to Nuclear Medicine Clinical Applications: Regulatory Standards and Harmonisation of Quality and Safety”, held in February 2022, provided the basis for this document, which gives guidance for the early phase clinical research with novel radionuclides. It describes the current standards and a harmonised view of the European regulatory framework. The document complements the existing regulatory framework and is not considered legally binding. Six chapters cover different aspects in radiopharmaceutical development. Each chapter includes dedicated guidelines and guidance documents from regulatory authorities and professional organisations, as well as references to scientific publications on the respective topic. An introduction of PRISMAP and the project scope is followed by a definition of terms and nomenclature for specification of novel radionuclides within PRISMAP. The following chapter focuses on the production of radionuclides and implementation of GMP in the radiopharmaceutical development process. It provides relevant definitions and gives recommendations where GMP compliant processes should be introduced in the production of novel radionuclides. Guidance for controls of radionuclides including starting materials, process validation, in-process controls, chemical precursors and production of radiopharmaceuticals are briefly addressed. The subsequent chapter covers quality specifications and quality control. It includes details on relevant European Pharmacopoeia texts and guidance for compliance, summarises other regulatory texts from the EMA and ICH, giving general considerations on specifications and specific guidance for validation of analytical methods. It provides definitions on drug substance and drug product and addresses all relevant specific quality criteria for novel radionuclides. The next chapter deals with metrology and medical physics aspects in clinical translation. The relation to the Basic Safety Standards of the Council Directive 2013/59/Euratom is described, which includes aspects of therapy planning and dosimetry for novel radionuclides. Standardisation in relation to traceability is addressed in a dedicated part on Metrology. The role of Medical Physics in the context of standardisation and harmonisation of the clinical use of novel radionuclides for imaging equipment, image acquisition, processing parameters, and quality control implementation of new technologies is summarised. The final chapter covers Non-Clinical Safety and Pharmacology aspects and provides an overview of the current guidance documents to assess preclinical dosimetry, toxicity (new EMA guideline specific for radiopharmaceuticals), and pharmacology of radiopharmaceuticals, which are developed with the aim to be used in human clinical trials. Recent specific guidance documents on this topic, particularly from the IAEA are summarised and included. This guidance document serves as an essential and comprehensive guide for radionuclide producers, radiopharmaceutical translational scientists, clinical and hospital based radiopharmaceutical development researchers through the complex jungle of pharmaceutical regulations and guidelines. It provides a harmonised view to standardise data required for clinical translation of novel radionuclides.

Published
2022
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17. Therapeutic efficacy of

Author

Mehrdad, Khoshnevis, Richard, Brown, Sara, Belluco, Ilyes, Zahi, Luca, Maciocco, Catherine, Bonnefont-Rebeix, Elodie, Pillet-Michelland, Jonathan, Tranel, Thierry, Roger, Christophe, Nennig, Patrick, Oudoire, Lionel, Marcon, Olivier, Tillement, Cédric, Louis, Hélène, Gehan, Manuel, Bardiès, Maurizio, Mariani, Valeria, Muzio, Jean-Philippe, Meunier, Charlotte, Duchemin, Nathalie, Michel, Estelle, N'Tsiba, Ferid, Haddad, Thierry, Buronfosse, Claude, Carozzo, and Frédérique, Ponce

Abstract

Glioblastoma is considered the most common malignant primary tumor of central nervous system. In spite of the current standard and multimodal treatment, the prognosis of glioblastoma is poor. For this reason, new therapeutic approaches need to be developed to improve the survival time of the glioblastoma patient. In this study, we performed a preclinical experiment to evaluate therapeutic efficacy of

Published
2022

18. How radiolysis impacts astatine speciation?

Author

Mohammad Ghalei, Parastoo Mahdi Khoshouei, Johan Vandenborre, François Guerard, Guillaume Blain, Mojtaba Zarei, Ferid Haddad, Massoud Fattahi, Guérard, François, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nuclear Oncology (CRCI2NA / Eq 2), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), GIP ARRONAX [Nantes], and Université de Nantes (UN)

Subjects
Radiation, Hydrogen Chloride, [SDV.CAN] Life Sciences [q-bio]/Cancer, Radiolysis, Astatine Chemistry, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chloroform, G-yield
Abstract

International audience; This work deals with the impact of chloroform radiolysis on astatine chemistry. Astatine-211 is a promising radionuclide for the targeted alpha therapy of cancers. Yet, the production of 211 At based radiopharmaceuticals is often complicated by radiolysis due to its own decay, leading to solvent degradation and then impacting astatine chemical state and radiolabeling efficiency. A better understanding of the radiolysis phenomenon is thus necessary. Two experiments are performed: (1) pH measurement during the At extraction in chloroform medium, (2) pH determination calculated from the HCl chemical yield which is obtained during the radiolysis of chloroform medium by γ-ray. In both cases, the pH values are determined at 2.0 ± 0.5. Then, it is possible to predict the acidic conditions during the 211 At production by HCl radiolytic yield determination. This work demonstrated that the radiolysis induced by At during its production in CHCl3 medium should be taken into account as it has a significant effect on acid-basic conditions. The work helps understanding the mechanisms of production of a major impurity generated from 211 At radiolysis in chloroform which alters its radiochemistry, allowing for the identification of solutions to counteract these unwanted effects.

Published
2022
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19. Technical note: Proton beam dosimetry at ultra-high dose rates (FLASH): Evaluation of GAFchromic™ (EBT3, EBT-XD) and OrthoChromic (OC-1) film performances

Author

Daphnée Villoing, Charbel Koumeir, Arthur Bongrand, Arnaud Guertin, Ferid Haddad, Vincent Métivier, Freddy Poirier, Vincent Potiron, Noël Servagent, Stéphane Supiot, Grégory Delpon, and Sophie Chiavassa

Subjects
Film Dosimetry, Calibration, Proton Therapy, General Medicine, Protons, Radiometry
Abstract

The ARRONAX cyclotron facility offers the possibility to deliver proton beams from low to ultra-high dose rates (UHDR). As a good control of the dosimetry is a prerequisite of UHDR experimentations, we evaluated in different conditions the usability and the dose rate dependency of several radiochromic films commonly used for dosimetry in radiotherapy.We compared the dose rate dependency of three types of radiochromic films: GAFchromic™ EBT3 and GAFchromic™ EBT-XD (Ashland Inc., Wayne, NJ, USA), and OrthoChromic OC-1 (OrthoChrome Inc., Hillsborough, NJ, USA), after proton irradiations at various mean dose rates (0.25, 40, 1500, and 7500 Gy/s) and for 10 doses (2-130 Gy). We also evaluated the dose rate dependency of each film considering beam structures, from single pulse to multiple pulses with various frequencies.EBT3 and EBT-XD films showed differences of response between conventional (0.25 Gy/s) and UHDR (7500 Gy/s) conditions, above 10 Gy. On the contrary, OC-1 films did not present overall difference of response for doses except below 3 Gy. We observed an increase of the netOD with the mean dose rate for EBT3 and EBT-XD films. OC-1 films did not show any impact of the mean dose rate up to 7500 Gy/s, above 3 Gy. No difference was found based on the beam structure, for all three types of films.EBT3 and EBT-XD radiochromic films should be used with caution for the dosimetry of UHDR proton beams over 10 Gy. Their overresponse, which increases with mean dose rate and dose, could lead to non-negligible overestimations of the absolute dose. OC-1 films are dose rate independent up to 7500 Gy/s in proton beams. Films response is not impacted by the beam structure. A broader investigation of the usability of OC-1 films in UHDR conditions should be conducted at intermediate and higher mean dose rates and other beam energies.

Published
2021

21. New results on proton-induced reactions on vanadium for Sc47 production and the impact of level densities on theoretical cross sections

Author

G. Pupillo, Luciano Canton, L. De Dominicis, Liliana Mou, M.P. Carante, Ferid Haddad, F. Barbaro, Adriano Fontana, and A. Colombi

Subjects
Physics, chemistry, Proton, 010308 nuclear & particles physics, 0103 physical sciences, Vanadium, chemistry.chemical_element, Production (computer science), Atomic physics, 010306 general physics, 01 natural sciences, Excitation, 3. Good health
Abstract

New data for the ${}^{\text{nat}}\mathrm{V}(p,x)$ reactions have been measured in the range 26--70 MeV, with production of the nuclides $^{47}\mathrm{Sc}, ^{43}\mathrm{Sc}, {}^{44m}\mathrm{Sc}, {}^{44g}\mathrm{Sc}, ^{46}\mathrm{Sc}, ^{48}\mathrm{Sc}, ^{42}\mathrm{K}, ^{43}\mathrm{K}, ^{48}\mathrm{V}, ^{48}\mathrm{Cr}, ^{49}\mathrm{Cr}$, and $^{51}\mathrm{Cr}$. The focus is on the production of $^{47}\mathrm{Sc}$, a ${\ensuremath{\beta}}^{\ensuremath{-}}$ emitter suitable for innovative radiotheranostic applications in nuclear medicine. The measured cross sections for this radionuclide and its contaminants are compared with the theoretical excitation functions calculated with the talys code. In view of novel radiopharmaceutical applications, it is essential to accurately describe these cross sections for the evaluation of yields, purities, and dose releases. Hence, we optimize the level-density parameters of the microscopic models in the talys code to obtain the best possible descriptions of the new data. We consider different irradiation conditions to estimate the production yields from the cross sections determined in this paper.

Published
2021
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22. Production of 67Cu by enriched 70Zn targets: first measurements of formation cross sections of 67Cu, 64Cu, 67Ga, 66Ga, 69mZn and 65Zn in interactions of 70Zn with protons above 45 MeV

Author

Juan Esposito, G. Pupillo, Liliana Mou, Ferid Haddad, Micol Pasquali, Alessandra Boschi, Petra Martini, Adriano Duatti, and Gianfranco Cicoria

Subjects
Nuclear reaction, 03 medical and health sciences, 0302 clinical medicine, Chemistry, Radiochemistry, Physical and Theoretical Chemistry, 010403 inorganic & nuclear chemistry, 01 natural sciences, 030218 nuclear medicine & medical imaging, 0104 chemical sciences
Abstract

Despite its insufficient availability, Copper-67 is currently attracting much attention for its enormous potential for cancer therapy as theranostic radionuclide. This work aims to accurately measure the unexplored cross section 70Zn(p,x)67Cu in the energy range 45–70 MeV and to evaluate its potential advantages in the case of high-intensity proton beams provided by compact cyclotrons. Thin target foils of enriched 70Zn were manufactured by lamination at the INFN-LNL and irradiated at the ARRONAX facility using the stacked-foils method. A radiochemical procedure for the separation of Cu, Ga and Zn contaminants and the isolation of 67Cu from the irradiated material was developed. The efficiency of the chemical processing was determined for each foil by monitoring the activity of selected tracer radionuclides (61Cu, 66Ga and 69mZn) through γ-spectrometry. Experimental data of the 70Zn(p,x)67Cu, 64Cu, 67Ga, 66Ga, 69mZn, 65Zn cross sections were measured for the first time in the energy range 45–70 MeV and compared with the theoretical results obtained by using the TALYS code. The 67Cu production yield by using enriched 70Zn thick targets was compared with the results obtained by using 68Zn targets in the same irradiation conditions.

Published
2020
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25. New excitation functions measurement of nuclear reactions induced by deuteron beams on yttrium with particular reference to the production of 89Zr

Author

Simone Manenti, Flavia Groppi, Ferid Haddad, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Cyclotron ARRONAX, GIP, Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)

Subjects
Nuclear reaction, Cross-section, Yield, Nuclear and High Energy Physics, Materials science, Zr radioisotopes, Cyclotron, 89Zr, chemistry.chemical_element, 01 natural sciences, 7. Clean energy, law.invention, 03 medical and health sciences, Cross section (physics), 0302 clinical medicine, law, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, 0103 physical sciences, Instrumentation, [PHYS]Physics [physics], 010308 nuclear & particles physics, Activation technique, Yttrium, 89 Zr, chemistry, Deuterium, 030220 oncology & carcinogenesis, Yield (chemistry), Deuteron irradiation, Atomic physics, Yttrium target, Excitation
Abstract

International audience; We investigated 89Zr production induced by deuteron beams on yttrium targets at energies up to Ed = 32 MeV using the stacked-foil activation technique. Cross sections of the following nuclear reactions 89Y(d,2n)89Zr, 89Y(d,3n)88Zr and 89Y(d,x)88Y have also been measured. Based on the measured values, we determined the thick target yields for 89Zr and 88Zr which is the main contaminant associated to the production of 89Zr.

Published
2019
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26. A Monte Carlo Determination of Dose and Range Uncertainties for Preclinical Studies with a Proton Beam

Author

Daphnée Villoing, Sophie Chiavassa, Arthur Bongrand, Arnaud Guertin, Gregory Delpon, Vincent Potiron, Stéphane Supiot, Ferid Haddad, Noël Servagent, Charbel Koumeir, Freddy Poirier, Vincent Métivier, Cyclotron ARRONAX, GIP, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)

Subjects
[PHYS]Physics [physics], Cancer Research, Range (particle radiation), Materials science, Proton, Nuclear engineering, Monte Carlo method, Context (language use), dose calculation, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Tumor response, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, radiation dosimetry, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Absorbed dose, proton therapy, preclinical studies, Proton therapy, Beam (structure), Monte Carlo simulation
Abstract

Simple Summary If reference studies can be found on the uncertainties linked to the clinical context of proton therapy, they, although equally critical, are very patchy in a preclinical context, and are specific to each beam line. This work provides the community with a complete assessment of the sources of uncertainties for a preclinical proton beam line. This aims to ensure that, in this line, the biological results observed and the dose–response relationships are obtained without any bias. Despite being specific to a preclinical line, the results presented here can be transposed to other types of proton preclinical facilities, and thus allow us to effectively compare them to one another. Abstract Proton therapy (PRT) is an irradiation technique that aims at limiting normal tissue damage while maintaining the tumor response. To study its specificities, the ARRONAX cyclotron is currently developing a preclinical structure compatible with biological experiments. A prerequisite is to identify and control uncertainties on the ARRONAX beamline, which can lead to significant biases in the observed biological results and dose–response relationships, as for any facility. This paper summarizes and quantifies the impact of uncertainty on proton range, absorbed dose, and dose homogeneity in a preclinical context of cell or small animal irradiation on the Bragg curve, using Monte Carlo simulations. All possible sources of uncertainty were investigated and discussed independently. Those with a significant impact were identified, and protocols were established to reduce their consequences. Overall, the uncertainties evaluated were similar to those from clinical practice and are considered compatible with the performance of radiobiological experiments, as well as the study of dose–response relationships on this proton beam. Another conclusion of this study is that Monte Carlo simulations can be used to help build preclinical lines in other setups.

Published
2021
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27. Bremsstrahlung X-rays as a non-invasive tool for ion beam monitoring

Author

Quentin Mouchard, Noël Servagent, Ferid Haddad, Arnaud Guertin, Vincent Métivier, F. Ralite, Charbel Koumeir, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Cyclotron ARRONAX, and GIP

Subjects
Nuclear and High Energy Physics, Materials science, Ion beam, Astrophysics::High Energy Astrophysical Phenomena, Physics::Medical Physics, Ion beam monitoring, Signal, 030218 nuclear medicine & medical imaging, Ion, 03 medical and health sciences, 0302 clinical medicine, Optics, Dosimetry, X-rays, Irradiation, Nuclear Experiment, Instrumentation, [PHYS]Physics [physics], business.industry, Non invasive, Bremsstrahlung, Radiobiology, Bremssstrahlung, 030220 oncology & carcinogenesis, Physics::Accelerator Physics, business, Sensitivity (electronics), Beam (structure)
Abstract

International audience; Non-invasive beam monitoring tools are required to guarantee the delivered dose during ion irradiation. Measuring bremsstrahlung X-rays emitted directly from the irradiated medium is a promising approach. This work presents the feasibility of the method for different incident particles with different energies. A PMMA target was bombarded with helium ions of 68 MeV and protons beams of 30, 40, and 50 MeV. The bremsstrahlung signal, measured with a SDD, was in the magnitude of 10 4 X-rays/nC, indicating the significant sensitivity of the method. A good agreement was found (

Published
2021
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29. First laser ions at the CERN-MEDICIS facility

Author

Klaus Wendt, Pascale Fernier, Shane Wilkins, Annie Ringvall Moberg, Vincent Barozier, Felix Weber, Ermanno Barbero, Vadim Maratovich Gadelshin, Thomas Elias Cocolios, Thierry Stora, Dominik Studer, Eric Chevallay, Andres Vieitez Suarez, Kristof Dockx, Ana Paula Bernardes, B. Crepieux, Matthias Eck, Ferid Haddad, Roberto Formento Cavaier, Johannes Jakobi, Sebastian Rothe, J.P. Ramos, S. Marzari, Laura Lambert, B. A. Marsh, Valentin Fedosseev, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public)

Subjects
Nuclear and High Energy Physics, Materials science, Nuclear engineering, TERBIUM, NUCLEAR MEDICINE, 030218 nuclear medicine & medical imaging, Isotope separation, law.invention, Ion, 03 medical and health sciences, 0302 clinical medicine, law, LASER RESONANCE IONIZATION, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Physical and Theoretical Chemistry, THERANOSTICS, Large Hadron Collider, Condensed Matter Physics, Laser, Mass separation, CERN MEDICIS, Atomic and Molecular Physics, and Optics, Ion source, 3. Good health, RADIOACTIVE ION BEAM, 030220 oncology & carcinogenesis, Resonance ionization, ISOTOPE SEPARATION, Other
Abstract

The CERN-MEDICIS facility aims to produce emerging medical radionuclides for the theranostics approach in nuclear medicine with mass separation of ion beams. To enhance the radioisotope yield and purity of collected samples, the resonance ionization laser ion source MELISSA was constructed, and provided the first laser ions at the facility in 2019. Several operational tests were accomplished to investigate its performance in preparation for the upcoming production of terbium radioisotopes, which are of particular interest for medical applications. © 2020, The Author(s). KU Leuven Horizon 2020: 642889 MEDICIS-PROMED 05P12UMCIA, 05P15UMCIA Open Access funding provided by Projekt DEAL. We would like to acknowledge the help and assistance from the whole MEDICIS collaboration; from CERN-ISOLDE Technical and Physical groups. This research project has been supported by a Marie Skłodowska-Curie Innovative Training Network Fellowship of the European Commission’s Horizon 2020 Programme under contract number 642889 MEDICIS-PROMED; by the German Federal Ministry of Education and Research under the consecutive projects 05P12UMCIA and 05P15UMCIA; by the Research Foundation Flanders FWO (Belgium) and by a KU Leuven START grant.

Published
2020
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30. Thick multi-layers analysis using high energy PIXE

Author

Alexandre Subercaze, Noël Servagent, Ferid Haddad, Arnaud Guertin, Charbel Koumeir, Vincent Métivier, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public)

Subjects
010302 applied physics, Nuclear and High Energy Physics, High energy, Ion beam analysis, Materials science, Cyclotron, Analytical chemistry, Multi-layers, 010403 inorganic & nuclear chemistry, 01 natural sciences, 0104 chemical sciences, law.invention, High energy PIXE, law, 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Instrumentation
Abstract

A method for multi-layer analysis using high energy PIXE is described. It is based on the variation of the K α K β ratio as a function of the detection angle. Experiments have been carried out at the ARRONAX cyclotron using 70 MeV protons in order to validate this method. The thicknesses and the sequences of simple multi-layers targets and more complex targets with hidden layers have been determined using this method.

Published
2017
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31. Excitation function and yield for the 103Rh(d,2n)103Pd nuclear reaction: Optimization of the production of palladium-103

Author

Flavia Groppi, C. Duchemin, Giulio Cotogno, Ferid Haddad, Uwe Holzwarth, Simone Manenti, María del Carmen Alí Santoro, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Joint Research Centre, European Commission [Brussels], Università degli Studi di Milano [Milano] (UNIMI), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), and ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011)

Subjects
Excitation function, Nuclear reaction, Cancer Research, Radiochemistry, chemistry.chemical_element, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 010403 inorganic & nuclear chemistry, 01 natural sciences, 7. Clean energy, 030218 nuclear medicine & medical imaging, 0104 chemical sciences, Rhodium, 03 medical and health sciences, 0302 clinical medicine, chemistry, Deuterium, Isotopes of palladium, Yield (chemistry), Molecular Medicine, Physical chemistry, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, Excitation, Palladium
Abstract

Deuteron-induced nuclear reactions for the generation of 103Pd were investigated using the stacked-foil activation technique on rhodium targets at deuteron energies up to Ed=33MeV. The excitation functions of the reactions 103Rh(d,xn)101,103Pd, 103Rh(d,x)100g,cum,101m,g,102m,gRh and 103Rh(d,2p)103Ru have been measured, and the Thick-Target Yield for 103Pd has been calculated.

Published
2017
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32. New results on the V(p,x)43Sc cross section: Analysis of the discrepancy with previous data

Author

Adriano Fontana, Luciano Canton, Ferid Haddad, Liliana Mou, G. Pupillo, Laboratori Nazionali di Legnaro (LNL), Istituto Nazionale di Fisica Nucleare (INFN), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Istituto Nazionale di Fisica Nucleare, Sezione di Pavia (INFN), and Istituto Nazionale di Fisica Nucleare, Sezione di Padova (INFN, Sezione di Padova)

Subjects
Nuclear reaction, Physics, Nuclear and High Energy Physics, 010308 nuclear & particles physics, 010403 inorganic & nuclear chemistry, 01 natural sciences, 0104 chemical sciences, Nuclear physics, 0103 physical sciences, Extensive data, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Cross section analysis, Instrumentation, ComputingMilieux_MISCELLANEOUS
Abstract

This work deals with the new cross section data obtained for the natV(p,x)43Sc nuclear reaction. We focus on this specific channel because we found a significant discrepancy with a recent NIM B publication, reporting extensive data on activation cross-sections induced by proton-Vanadium collisions up to 65 MeV. Proton-irradiation and γ -spectrometry were performed at ARRONAX facility (Nantes, France) by means of activation of stacked-foils targets up to 70 MeV. Our new experimental values are compared with all the previous measurements and supported by the results obtained with the reaction codes FLUKA, EMPIRE and TALYS. A discussion is given about the possible origin of the observed discrepancy.

Published
2020
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33. ARRONAX Cyclotron: Setting up of In-HouseHospital Radiopharmacy

Author

Ferid Haddad, C. Bourdeau, Aurélien Vidal, Tracy Garcia, Mathieu Frindel, Mickaël Bourgeois, Alain Faivre-Chauvet, Bernardo, Elizabeth, Cyclotron ARRONAX [Saint-Herblain], ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
0301 basic medicine, medicine.medical_specialty, Article Subject, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Medical physics, General Immunology and Microbiology, business.industry, General Medicine, 3. Good health, Clinical trial, 030104 developmental biology, Facility Design and Construction, 030220 oncology & carcinogenesis, Medicine, Nuclear Medicine, Radiopharmaceuticals, Pharmacy Service, Hospital, business, Research Article
Abstract

International audience; Whilst radiopharmaceuticals have an important role to play in both imaging and treatment of patients, most notably cancer patients, nuclear medicine and radiopharmacy are currently facing challenges to create innovative new drugs. Traditional radiopharmaceutical manufacture can be considered as either a routine hospital production or a large-scale industrial production. The gap between these two practices has meant that there is an inability to supply innovative radiopharmaceuticals for use at the local level for mono-or multicentric clinical trials with satisfactory quality and safety specifications. This article highlights the regulatory requirements in aseptic pharmaceutical processing and in nuclear medicine to be able to locally produce radiopharmaceuticals. We validate the proof-of-concept for an "in-house" hospital-based radiopharmacy including an on-site cyclotron, that can fulfill the conflicting requirements between radiation safety and aseptic processing. The ARRONAX in-house radiopharmacy is currently able to provide sterile and pyrogenic-free injectable radiopharmaceutical compounds for both industrial and institutional clinical trials.

Published
2020
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34. Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease

Author

Ferid Haddad, François Guérard, Françoise Kraeber-Bodéré, Joëlle Gaschet, Delphine Dansette, Sébastien Gouard, Romain Eychenne, Séverine Marionneau-Lambot, Nicolas Chouin, Catherine Maurel, Cyril Alliot, Michel Chérel, Clément Bailly, Bernardo, Elizabeth, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), CH Départemental Vendée, École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Département d'oncologie médicale [Saint Herblain] (Centre René Gauducheau - ICO), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)

Subjects
0301 basic medicine, Cancer Research, Radioimmunoconjugate, [SDV.CAN]Life Sciences [q-bio]/Cancer, Targeted alpha therapy, lcsh:RC254-282, Article, 03 medical and health sciences, CD138, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Elotuzumab, Survival rate, Multiple myeloma, biology, business.industry, Daratumumab, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Minimal residual disease, 3. Good health, multiple myeloma, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Toxicity, Cancer research, biology.protein, minimal residual disease, Antibody, business, astatine-211, medicine.drug
Abstract

International audience; Simple Summary:Multiple myeloma is a cancer that remains incurable. Among the many therapies under evaluation, antibodies can be used as vehicles to target and deliver toxic radiation to the tumour cells. Our objective was therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 mAb with astatine-211, to destroy the residual cells responsible for relapse. We have shown in a mouse model that mimics human disease, that destroying multiple myeloma cells is feasible with low toxicity by injecting an anti-CD138 mAb coupled with astatine-211. This approach could eradicate residual cells after initial treatment and thus prevent recurrence. Abstract: Despite therapeutic progress in recent years with the introduction of targeted therapies (daratumumab, elotuzumab), multiple myeloma remains an incurable cancer. The question is therefore to investigate the potential of targeted alpha therapy, combining an anti-CD138 antibody with astatine-211, to destroy the residual cells that cause relapses. A preclinical syngeneic mouse model, consisting of IV injection of 1 million of 5T33 cells in a KaLwRij C57/BL6 mouse, was treated 10 days later with an anti-mCD138 antibody, called 9E7.4, radiolabeled with astatine-211. Four activities of the 211 At-9E7.4 radioimmunoconjugate were tested in two independent experiments: 370 kBq (n = 16), 555 kBq (n = 10), 740 kBq (n = 17) and 1100 kBq (n = 6). An isotype control was also tested at 555 kBq (n = 10). Biodistribution, survival rate, hematological parameters, enzymatic hepatic toxicity, histological examination and organ dosimetry were considered. The survival median of untreated mice was 45 days after engraftment. While the activity of 1100 kBq was highly toxic, the activity of 740 kBq offered the best efficacy with 65% of overall survival 150 days after the treatment with no evident sign of toxicity. This work demonstrates the pertinence of treating minimal residual disease of multiple myeloma with an anti-CD138 antibody coupled to astatine-211.

Published
2020
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35. Radionuclide candidates for β+γ coincidence PET: An overview

Author

Mateusz Sitarz, Jean-Pierre Cussonneau, Tomasz Matulewicz, Ferid Haddad, University of Warsaw (UW), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
Novel technique, Physics, Radionuclide, Radiation, Modality (human–computer interaction), medicine.diagnostic_test, Astrophysics::High Energy Astrophysical Phenomena, Physics::Medical Physics, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Cyclotrons, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 010403 inorganic & nuclear chemistry, 01 natural sciences, Coincidence, β+γ coincidence, 030218 nuclear medicine & medical imaging, 0104 chemical sciences, Nuclear physics, 03 medical and health sciences, 0302 clinical medicine, PET, Positron emission tomography, medicine, Production of medical radionuclides
Abstract

International audience; Following the advancement of the Positron Emission Tomography (PET), a novel technique emerged which takes advantage of the gamma quanta emitted, in some cases, after the β+ decay. While 44gSc is commonly agreed the best choice to validate this new modality, other radioisotopes must also be considered in the future. We present them in this paper, along with their possible applications, properties and the optimal production routes with the use of the accelerators.

Published
2020
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36. Medical applications of diamond detectors: online control of Hadrontherapy with fast timing and Microbeam Radiation Therapy monitoring

Author

Denis Dauvergne, Abbassi, L., Jean-François Adam, Bes, A., Bosson, G., Collot, J., Crozes, T., Curtoni, S., Gallin-Martel, L., L Gallin-Martel, M., Ghimouz, A., Ferid Haddad, Charbel Koumeir, Lacoste, A., Jean Michel Létang, Jayde Livingstone, Marcatili, S., Vincent Métivier, F Motte, J., F Muraz, J., Rarbi, F. E., Rossetto, O., Rosuel, N., Noël Servagent, É, Testa, Tribouilloy, L., Yamouni, M., Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Nanofab (Nanofab ), Institut Néel (NEEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Synchrotron Radiation for Biomedicine Laboratory (STROBE), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire SUBATECH Nantes (SUBATECH), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Nantes (UN)-Mines Nantes (Mines Nantes), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics::Instrumentation and Detectors, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det]
Abstract

International audience; This presentation will focus on two applications of diamond detectors in the field of innovative radiotherapies.The first one consists of a beam hodoscope for hadrontherapy (proton or carbon ion beams). This detector will be used for position and time stamp of the incident particle beam, in order to detect secondary particles (mainly prompt-gammas). Time of Flight is used to reduce background from massive particles, and select photons issued from the patient only. This detector will be made of a mosaic assembly of several diamond plates with double-side strip metallization. The electronic readout design will enable high count rate and high time resolution of the detector.Preliminary measurements were performed at ARRONAX with 68 MeV protons. Detection efficiency was measured with mono- and polycrystalline diamond detectors. For the latter, up to 95% efficiency (corrected from noise triggering) was obtained for single-proton detection. The time resolution was close to 100ps rms for prompt gamma detection using diamond and fast scintillators for incoming particles and secondary photon detection, respectively. The potential for ultra-fast timing in prompt gamma imaging leads to spatial discrimination and real time reconstruction capabilities for range verification during treatment.The second application consists in the in vivo monitoring of Microbeam Radiation Therapy. The beam is spatially fractionated with local doses above 1000 Gy/s delivered in narrow peaks of a few tens of μm, separated by 300-500μm. A large area diamond detector with 1D position readout by fast- and high-dynamics charge integration will be used to monitor the transmitted photon beam, and thus evaluate the energy deposited in the patient.

Published
2019

37. Can We Extract Production Cross-Sections from Thick Target Yield Measurements? A Case Study Using Scandium Radioisotopes

Author

Tomasz Matulewicz, Jerzy Jastrzębski, Ferid Haddad, Katarzyna Szkliniarz, W. Zipper, Mateusz Sitarz, GIP ARRONAX, Université de Nantes (UN), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, and University of Warsaw (UW)

Subjects
Materials science, numerical analysis, Analytical chemistry, chemistry.chemical_element, radioisotope production, 010403 inorganic & nuclear chemistry, 01 natural sciences, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, cross-section reconstruction, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, thick target yield measurements, lcsh:Nuclear and particle physics. Atomic energy. Radioactivity, Scandium, Instrumentation, ComputingMilieux_MISCELLANEOUS, Excitation function, [PHYS]Physics [physics], Numerical analysis, Function (mathematics), lcsh:QC1-999, 0104 chemical sciences, chemistry, Yield (chemistry), medical Sc radioisotopes, lcsh:QC770-798, Production (computer science), lcsh:Physics
Abstract

In this work, we present an attempt to estimate the reaction excitation function based on the measurements of thick target yield. We fit a function to experimental data points and then use three fitting parameters to calculate the cross-section. We applied our approach to 43Ca(p,n)43Sc, 44Ca(p,n)44gSc, 44Ca(p,n)44mSc, 48Ca(p,2n)47Sc and 48Ca(p,n)48Sc reactions. A general agreement was observed between the reconstructions and the available cross-section data. The algorithm described here can be used to roughly estimate cross-section values, but it requires improvements.

Published
2019
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38. What is the Best Radionuclide for Immuno-PET of Multiple Myeloma? A Comparison Study Between

Author

Clément, Bailly, Sébastien, Gouard, François, Guérard, Benjamin, Chalopin, Thomas, Carlier, Alain, Faivre-Chauvet, Patricia, Remaud-Le Saëc, Mickaël, Bourgeois, Nicolas, Chouin, Latifa, Rbah-Vidal, Raphaël, Tripier, Ferid, Haddad, Françoise, Kraeber-Bodéré, Caroline, Bodet-Milin, and Michel, Chérel

Subjects
Radioisotopes, copper-64, zirconium-89, Antibodies, Monoclonal, Bone Neoplasms, Article, Cell Line, Mice, Inbred C57BL, multiple myeloma, Mice, Copper Radioisotopes, Fluorodeoxyglucose F18, Cell Line, Tumor, Positron-Emission Tomography, immuno-PET, murine CD138, Animals, Female, Tissue Distribution, Syndecan-1, Zirconium, Radiopharmaceuticals
Abstract

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr’s tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.

Published
2019

39. New Cross-Sections for natMo(α,x) Reactions and Medical 97Ru Production Estimations with Radionuclide Yield Calculator

Author

Arnaud Guertin, Mateusz Sitarz, Ferid Haddad, Tomasz Matulewicz, Etienne Nigron, GIP ARRONAX, Université de Nantes (UN), University of Warsaw (UW), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]

Subjects
Nuclear reaction, cross-section, Materials science, Cyclotron, Single-photon emission computed tomography, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 7. Clean energy, 01 natural sciences, 030218 nuclear medicine & medical imaging, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, 0103 physical sciences, medicine, Gamma spectroscopy, lcsh:Nuclear and particle physics. Atomic energy. Radioactivity, Irradiation, medical radioisotope production, cyclotron, stacked-foils, 010306 general physics, Instrumentation, Radionuclide, medicine.diagnostic_test, Radionuclide Yield Calculator, Radiochemistry, lcsh:QC1-999, Yield (chemistry), SPECT, thick target yield, gamma spectroscopy, lcsh:QC770-798, radioactive impurities, Beam (structure), lcsh:Physics
Abstract

The production of 97Ru, a potential Single Photon Emission Computed Tomography (SPECT) radioisotope, was studied at ARRONAX. The cross-section of natMo(&alpha, x)97Ru reaction was investigated in the range of 40&ndash, 67 MeV irradiating the natMo and Al stacked-foils. The activities of 97Ru and other radioactive contaminants were measured via gamma spectroscopy technique. A global good agreement is observed between obtained cross-section results, previously reported values and TENDL-2017 predictions. Additionally, Radionuclide Yield Calculator, a software that we made available for free, dedicated to quickly calculate yields and plan the irradiation for any radioisotope production, was introduced. The yield of investigated nuclear reactions indicated the feasibility of 97Ru production for medical applications with the use of &alpha, beam and Mo targets opening the way to a theranostic approach with 97Ru and 103Ru.

Published
2019
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40. Overview of the Most Promising Radionuclides for Targeted Alpha Therapy: The 'Hopeful Eight'

Author

Michel Chérel, Jean-François Gestin, François Guérard, Romain Eychenne, Ferid Haddad, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), INCa-DGOS-Inserm_12558, ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), European Project: CA19114,NOAR, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Guérard, François, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID, and COST Action NOAR 'Network for Optimized Astatine labeled Radio-pharmaceuticals' - NOAR - CA19114 - INCOMING

Subjects
Radium-223, thorium-227, Computer science, [SDV]Life Sciences [q-bio], radium-223, Pharmaceutical Science, Alpha (ethology), Review, lead-212, actinium-225, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Pharmacy and materia medica, 0302 clinical medicine, medicine, Selection (genetic algorithm), targeted alpha therapy, terbium-149, α-emitters, 3. Good health, [SDV] Life Sciences [q-bio], RS1-441, 030220 oncology & carcinogenesis, Biochemical engineering, bismuth-213, astatine-211, Chemical design, bismuth-212, medicine.drug
Abstract

Among all existing radionuclides, only a few are of interest for therapeutic applications and more specifically for targeted alpha therapy (TAT). From this selection, actinium-225, astatine-211, bismuth-212, bismuth-213, lead-212, radium-223, terbium-149 and thorium-227 are considered as the most suitable. Despite common general features, they all have their own physical characteristics that make them singular and so promising for TAT. These radionuclides were largely studied over the last two decades, leading to a better knowledge of their production process and chemical behavior, allowing for an increasing number of biological evaluations. The aim of this review is to summarize the main properties of these eight chosen radionuclides. An overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.

Published
2021
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41. Carboxylate anion generation in aqueous solution from carbonate radiolysis, a potential route for abiotic organic acid synthesis on Earth and beyond

Author

G. Blain, Véronique Baty, Massoud Fattahi, A. Costagliola, Johan Vandenborre, Laurent Truche, Emeline Craff, Ferid Haddad, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER

Subjects
Molar concentration, Aqueous solution, 010504 meteorology & atmospheric sciences, Inorganic chemistry, 010502 geochemistry & geophysics, 01 natural sciences, 6. Clean water, Oxalate, chemistry.chemical_compound, Geophysics, chemistry, 13. Climate action, Space and Planetary Science, Geochemistry and Petrology, Radiolysis, Carbon dioxide, Earth and Planetary Sciences (miscellaneous), Carbonate, Formate, Carboxylate, [CHIM.RADIO]Chemical Sciences/Radiochemistry, Geology, 0105 earth and related environmental sciences
Abstract

Highlights • Carbonate radiolysis leads to successive formation of formate, acetate and oxalate. • H2 radiolytic production is significantly enhanced in the presence of carbonate. • Oxalate may reach the millimolar concentration level in deep ancient fracture fluids. • Carboxylates radiolytic production does not need catalyst or hydrothermal conditions. • These radiolytic by-products represent a source of energy for the deep biosphere. Low molecular weight carboxylate anions such as formate (HCOO−), acetate (CH3COO−) and oxalate (C2O ) have been shown to play an important role in supporting deep subsurface microbial ecosystems. Their origin whether biological or abiotic is currently highly debated, but surprisingly radiolytic production has rarely been considered, as it is the case for H2. Here, we address this question through dedicated irradiation experiments. Aqueous solutions containing carbonate, formate, acetate or oxalate have been irradiated using both the 60.7 MeV α-beam of the ARRONAX cyclotron (Nantes, France) and 661.7 keV γ-Ray in order to reveal the mechanism and chemical yield of radiation-induced dissolved carbonate degradation. The yields (G-values) of carboxylate anions production/degradation in low-concentration carbonate solution (0.01 to 1 mmol L−1) are measured. Carbonate degradation occurs through three consecutive steps (Carbonate Formate Acetate Oxalate) involving formate radical (CO2−•), dihydrogen (H2), and carbon dioxide (CO2) generation. Dissolved carbonate radiolysis provides a consistent pathway for both enhancing two-fold the radiolytic H2 production compared to pure water and generating carboxylic species, chiefly oxalate, readily available for microbes. Radiation-induced carbonate degradation may produce substantial amount (millimolar concentration) of carboxylate anions in ancient groundwaters from deep crystalline bedrocks. Subsurface lithoautotrophic microbial ecosystems may not only be supported by radiolytic H2 but also by carboxylate species from carbonate radiolysis. Carbonate radiolysis can be also an endogenous source of carboxylate species on Mars and other planetary bodies.

Published
2021
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42. Correction to: Production of 47Sc with natural vanadium targets: results of the PASTA project

Author

Alessandra Boschi, G. Pupillo, Luciano Canton, Sara Cisternino, Adriano Duatti, Ferid Haddad, Adriano Fontana, Simone Calzaferri, Hanna Skliarova, Micol Pasquali, Lucia De Dominicis, Petra Martini, Juan Esposito, and Liliana Mou

Subjects
Nuclear Energy and Engineering, Chemistry, Health, Toxicology and Mutagenesis, Environmental chemistry, Public Health, Environmental and Occupational Health, Production (economics), Vanadium, chemistry.chemical_element, Radiology, Nuclear Medicine and imaging, Pollution, Spectroscopy, Natural (archaeology), Analytical Chemistry
Published
2021
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43. Produire des radionucléides grâce à des accélérateurs : les cyclotrons

Author

Ferid Haddad

Abstract

Developpe aux Etats-Unis dans les annees 1930, le cyclotron est utilise aujourd’hui dans les grands hopitaux pour produire certains traceurs radioactifs a tres courte duree de vie (carbone 11, azote 13, fluor 18…). Ils permettent egalement de realiser de la radiotherapie externe et de la recherche nucleaire. 1 200 cyclotrons sont exploites a travers le monde, dont une vingtaine en France. Parmi eux, Arronax. Situe pres de Nantes, ce cyclotron unique au monde permet de produire des radionucleides innovants pour la recherche en medecine nucleaire, de mener des recherches sur les domaines de la radiolyse, la radiobiologie et la physique et d’assurer la formation des specialistes de demain dans le domaine de la production et l’utilisation des radionucleides medicaux.

Published
2016
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44. Speciation of technetium in carbonate media under helium ions and γ radiation

Author

Johan Vandenborre, Jérôme Roques, Massoud Fattahi, Frederic Poineau, Ferid Haddad, Pier-Lorenzo Solari, Mohammad Ghalei, G. Blain, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), University of Nevada [Las Vegas] (WGU Nevada), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], The authors would like to thank the ARRONAX staff for the efficient performing of irradiation runs in the cyclotron facility. The authors would like to thank SOLEIL synchrotron for provision of beam time using MARS beamline. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357., ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Synchrotron Soleil, DiffAbs beamline, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex, France (SYNCHROTRON SOLEIL, DIFFABS BEAMLINE, SAINT-AUBIN, BP 48, 91192 GIF-SUR-YVETTE CEDEX, FRANCE), and Synchrotron Soleil, DiffAbs beamline, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex, France

Subjects
γ radiation, Chemistry, Radiochemistry, chemistry.chemical_element, 02 engineering and technology, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 021001 nanoscience & nanotechnology, Technetium, 01 natural sciences, chemistry.chemical_compound, Helium ions, 0103 physical sciences, Genetic algorithm, Carbonate, Physical and Theoretical Chemistry, 010306 general physics, 0210 nano-technology, [CHIM.RADIO]Chemical Sciences/Radiochemistry, ComputingMilieux_MISCELLANEOUS
Abstract

Technetium carbonates complexes produced by chemical, electrochemical and radiolytic methods have been studied by UV-Visible, X-ray Absorption Fine Structure (XAFS) and Density Functional Theory methods. The (NH4)2TcCl6 salt was dissolved in 2 M KHCO3. The resulting purple solution was analyzed by XAFS and UV-Visible spectroscopy. The UV-Visible spectra exhibits a band centered at 515 nm. The XAFS results were consistent with the presence of polymeric species containing the [Tc2(μ−O)2]4+ core coordinated to carbonate ligand. Concerning the electrochemical methods, the pertechnetate anion was electrochemically reduced in concentrated carbonate solution [(CO3 2−)=5 M and (HCO3 −)=0.5 M]. For the radiolytic reduction, the speciation of Tc under Helium ions particle beam and γ radiation was examined by UV-Visible and XAFS spectroscopy in high concentrated carbonate media. In concentrated carbonate solutions, pertechnetate as Tc(VII), was not reduced under irradiation due to the formation of carbonate radical which is a strong oxidant. Then, the solution proposed was the addition of formate to the solution which can scavenge hydroxyl radical 10 times faster than carbonate and prevent re-oxidation of reduced technetium. The XANES and EXAFS spectroscopies, approved by theoretical methods, revealed that the final product of the radiolytic reduction of pertechnetate is in the +IV oxidation state. The final structure of the reduced product by He2+ radiolysis was the same as electrochemical reduction. From this complex determination and evolution vs. the dose, this study is reporting the solubility of the Tc(IV) complex.

Published
2019
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45. Production of $^{47}$Sc with natural vanadium targets: results of the PASTA project

Author

Alessandra Boschi, Juan Esposito, Adriano Duatti, Micol Pasquali, Petra Martini, Sara Cisternino, Lucia De Dominicis, G. Pupillo, Simone Calzaferri, Ferid Haddad, Hanna Skliarova, Liliana Mou, Luciano Canton, Adriano Fontana, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Cyclotron ARRONAX, GIP, and Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST)

Subjects
Nuclear reaction, Materials science, Health, Toxicology and Mutagenesis, Nuclear engineering, Vanadium, chemistry.chemical_element, 01 natural sciences, $^{47}$Sc, NO, 030218 nuclear medicine & medical imaging, Analytical Chemistry, 03 medical and health sciences, 0302 clinical medicine, Proton-induced reactions, 0103 physical sciences, Radiology, Nuclear Medicine and imaging, Theranostic radionuclides, Spectroscopy, $^{46}$Sc, [PHYS]Physics [physics], 010308 nuclear & particles physics, Public Health, Environmental and Occupational Health, Radioactive waste, Cyclotron-induced reactions, Pollution, Nuclear reaction codes, Nuclear Energy and Engineering, chemistry, Sc, 47
Abstract

International audience; The goal of PASTA project (acronym for production with accelerator of$^{47}$Sc for theranostic applications) is the determination of excitation functions associated to several nuclear reactions, aimed at yielding the theranostic radionuclide$^{47}$Sc. This work reports the main results obtained by irradiating natural vanadium targets with proton beams up to 70 MeV. Particular care is also given to the co-production of$^{46}$Sc, the only isotopic contaminant with half-life longer than$^{47}$Sc. Experimental results are compared with theoretical studies by means of known nuclear reaction software tools that are publicly available.

Published
2019
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46. Essai clinique autour d’un radiopharmaceutique innovant : le 64Cu-ATSM comme facteur prédictif de la réponse au traitement néo-adjuvant dans le cancer du rectum

Author

Ferid Haddad, Vincent Fleury, Aurélien Vidal, Michel Chérel, Mathilde Colombié, M. Frindel, Mickaël Bourgeois, F. Kraeber Bodéré, Caroline Rousseau, A. Rauscher, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), and Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
03 medical and health sciences, 0302 clinical medicine, Radiological and Ultrasound Technology, 030220 oncology & carcinogenesis, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Biophysics, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, 3. Good health, 030218 nuclear medicine & medical imaging
Abstract

Introduction Le 64Cu-ATSM est un medicament radiopharmaceutique (MRP) initialement developpe comme traceur TEP ciblant l’hypoxie tumorale, maintenant mieux defini comme traceur du stress oxydatif, etat lie a l’agressivite tumorale et les resistances au traitement. Notre essai clinique a pour but d’etudier, avec l’inclusion de 70 patients, la TEP-TDM au 64Cu-ATSM dans la prediction de la reponse au traitement neo-adjuvant dans le cancer du rectum. Methode Le 64Cu-ATSM est un complexe lipophile qui diffuse librement dans les membranes cellulaires. Sous l’effet du potentiel super-reducteur intracellulaire, le 64Cu est libere et s’accumule dans les cellules en etat de stress oxydatif. Le 64Cu est un emetteur B+ d’energie moy 278,2 keV, avec une T1/2 = 12,7 h. Etre autorise a utiliser ce MRP dans un essai clinique a necessite la redaction collaborative et multidisciplinaire d’un dossier du medicament experimental avec les equipes d’ARRONAX, cyclotron producteur de 64Cu, la Radiopharmacie de la PUI du CHU Nantes implantee dans ARRONAX et habilitee a delivrer les MRP en condition GMP et la Medecine Nucleaire de l’Institut de Cancerologie de l’Ouest. L’objectif principal est d’evaluer l’intensite de la fixation tumorale precoce du 64Cu-ATSM comme facteur predictif de la reponse histologique (estimee par un score de Rodel 3 ou 4) au traitement neo-adjuvant par radiochimiotherapie, dans le cancer du rectum localement avance. Les objectifs secondaires sont : etudier les intensites de fixation au temps tardif, les comparer avec la TEP-TDM au 18FDG, evaluer la correlation entre le 64Cu-ATSM et les marqueurs histopathologiques du stress oxydatif, evaluer la survie sans progression et mener une etude dosimetrique. Le bilan d’inclusion comprend une TEP-TDM au 18FDG, un TDM thoraco-abdomino-pelvienne et une IRM pelvienne. Pour la TEP-TDM au 64Cu-ATSM, 2 acquisitions sont realisees, centrees sur abdomen - pelvis, 1 h et 24 h apres injection. L’imagerie apres la fin de la radio-chimiotherapie comprend une TEP-TDM au 18FDG et une IRM pelvienne, avant chirurgie. Conclusion Cet essai clinique de phase II multicentrique, illustrant le developpement de MRP innovants, a ete autorise et a debute avec l’inclusion de 2 premiers patients, sans evenement indesirable signale. Les contraintes reglementaires liees au developpement de nouveaux MRP s’additionnent a celles de la recherche clinique, indispensables pour la securite, mais necessitant une approche interdisciplinaire.

Published
2020
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47. THE RADIOBIOLOGICAL PLATFORM AT ARRONAX

Author

Sébastien Gouard, Nathalie Michel, Nicolas Varmenot, Arnaud Guertin, Noël Servagent, Michel Chérel, Eric Garrido, Vincent Métivier, Viviana De Nadal, Roberto Cherubini, Thomas Sounalet, Freddy Poirier, Ferid Haddad, Charbel Koumeir, GIPARRONAX [Saint-Herblain, France], Laboratori Nazionali di Legnaro (LNL), Istituto Nazionale di Fisica Nucleare (INFN), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, This project is partially supported by the ‘Agence National de la Recherche’, called ‘Investissements d’Avenir’, Equipex ArronaxPlus n° ANR-11-EQPX-0004., ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Bernardo, Elizabeth, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Normandie Université (NU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique)

Subjects
[PHYS.NEXP] Physics [physics]/Nuclear Experiment [nucl-ex], Cyclotron, [SDV.CAN]Life Sciences [q-bio]/Cancer, Radiation, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 030218 nuclear medicine & medical imaging, law.invention, Nuclear physics, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, law, Humans, Radiology, Nuclear Medicine and imaging, Irradiation, Physics, Range (particle radiation), [PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Radiological and Ultrasound Technology, Public Health, Environmental and Occupational Health, Radiobiology, General Medicine, Alpha particle, Equipment Design, V79 cells, Cyclotrons, Charged particle, Beamline, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], France
Abstract

International audience; The cyclotron ARRONAX can deliver different types of particles (protons, deuterons, alpha-particles) in an energy range up to 68 MeV. One of its six experimental halls is dedicated to studying the interactions of radiation with matter including living matter. A horizontal beamline for cell irradiation has been setup and characterized. The radiobiological characterization was done in terms of V79 cells survival after irradiation with 68 MeV protons. The results demonstrate that radiobiological studies can be successfully performed confirming the high potential of the facility.

Published
2018
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48. Production of Sc medical radioisotopes with proton and deuteron beams

Author

M. Kisieliński, Jarosław Choiński, Malihe Rostampour, Aleksander Bilewicz, Kamil Kapinos, Jolanta Wojtkowska, Agnieszka Majkowska, Jerzy Jastrzębski, A. Trzcińska, Arnaud Guertin, Mateusz Sitarz, W. Zipper, Katarzyna Szkliniarz, A. Jakubowski, Anna Stolarz, Etienne Nigron, Rafał Walczak, Ferid Haddad, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), and ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011)

Subjects
Materials science, Proton, Cyclotron, (43-44-47)Sc radioisotopes, Generated impurities level, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 010403 inorganic & nuclear chemistry, 7. Clean energy, 01 natural sciences, Calcium Carbonate, 030218 nuclear medicine & medical imaging, law.invention, Proton and deuteron beams 43, 03 medical and health sciences, 0302 clinical medicine, law, 47 Sc radioisotopes Radioisotope production Thick Target Yield Generated impurities level, Humans, Radioisotope production, Radioisotopes, Titanium, Radiation, Thick Target Yield, Radiochemistry, Cyclotrons, Production efficiency, Deuterium, 0104 chemical sciences, Research centre, Yield (chemistry), Heavy ion, Proton and deuteron beams, Poland, Protons, Radiopharmaceuticals, Scandium
Abstract

Proton and deuteron beams (15.3 and 6.8 MeV, respectively) extracted from the PETtrace medical cyclotron at the Radiopharmaceuticals Production and Research Centre in the University of Warsaw, Heavy Ion Laboratory, 28 MeV protons from the C30 cyclotron at the National Centre for Nuclear Research, Świerk, near Warsaw and 33 MeV protons from the ARRONAX accelerator, Nantes were used to produce and investigate the medically interesting Sc radioisotopes. Both natural and isotopically enriched CaCO3 and TiO2 targets were used (42Ca, 43Ca, 44Ca, 48Ca, 48Ti). The production efficiency and isotopic purity were determined and are reported here for the highest commercially available enrichments of the target material. The Thick Target Yield, Activities at the End of Bombardment (EOB) and the relative activities of produced impurities at EOB are reported for 43Sc, 44gSc, 44mSc and 47Sc produced with particle energies below 33 MeV.

Published
2018
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49. Promising Scandium Radionuclides for Nuclear Medicine: A Review on the Production and Chemistry up to In Vivo Proofs of Concept

Author

Sandrine Huclier-Markai, Marie Mougin-Degraef, Ferid Haddad, Nicolas Chouin, Cyrille Alliot, Rabha Kerdjoudj, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), GIP ARRONAX [Nantes], Université de Nantes (UN), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Nuclear Oncology (CRCINA-ÉQUIPE 13), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Bernardo, Elizabeth

Subjects
Lanthanide, radiolabeling, Cancer Research, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lutetium, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, theranostic pair, Radiology, Nuclear Medicine and imaging, Scandium, Radionuclide Imaging, Pharmacology, Radioisotopes, Radionuclide, business.industry, Isotopes of scandium, General Medicine, 3. Good health, in vivo data, Oncology, chemistry, 030220 oncology & carcinogenesis, Positron-Emission Tomography, coordination chemistry, scandium isotopes, production, Nuclear Medicine, Radiopharmaceuticals, Nuclear medicine, business
Abstract

International audience; Scandium radionuclides have been identified in the late 1990s as promising for nuclear medicine applications, but have been set aside for about 20 years. Among the different isotopes of scandium, 43Sc and 44Sc are interesting for positron emission tomography imaging, whereas 47Sc is interesting for therapy. The 44Sc/47Sc or 43Sc/47Sc pairs could be thus envisaged as true theranostic pairs. Another interesting aspect of scandium is that its chemistry is governed by the trivalent ion, Sc3+. When combined with its hardness and its size, it gives this element a lanthanide-like behavior. It is then also possible to use it in a theranostic approach in combination with 177Lu or other lanthanides. This article aims to review the progresses that have been made over the last decade on scandium isotope production and coordination chemistry. It also reviews the radiolabeling aspects and the first (pre) clinical studies performed.

Published
2018
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50. Development of an ultra thin beam profiler for charged particle beams

Author

M. Verderi, Noël Servagent, F. Poirier, B. Boyer, C. Thiebaux, Frédéric Magniette, C. Koumeir, R. Cornat, M. Rubio Roy, Ferid Haddad, O. Gevin, Y. Geerebaert, Eric Delagnes, P. Manigot, Laboratoire Leprince-Ringuet (LLR), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Nucléaire et de Hautes Énergies (LPNHE (UMR_7585)), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Cyclotron ARRONAX, GIP, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), SPINtronique et TEchnologie des Composants (SPINTEC), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and ANR-17-CE31-0015,PEPITES,Développement d'un moniteur ultra-mince pour faisceau de particules chargées(2017)

Subjects
Physics, [PHYS]Physics [physics], Nuclear and High Energy Physics, Range (particle radiation), Protontherapy, business.industry, Cyclotron, Beam profiler, 01 natural sciences, Charged particle, 010305 fluids & plasmas, law.invention, Optics, law, Secondary emission, 0103 physical sciences, Laser beam quality, Thin film, 010306 general physics, business, Instrumentation, Radiation hardening, Beam (structure)
Abstract

Beam profiling during patient treatment in protontherapy requires ultra-thin monitors to preserve the high beam quality. For detectors upstream in the line, a material budget as low as ∼ 15 μ m water-equivalent is needed. In addition, the current trend of dose escalation to treat highly resistant tumors implies challenging requirements on monitor radiation hardness and dynamic range. We propose a new type of beam profiler, PEPITES, using secondary electron emission (SEE) and built with thin-film techniques. The beam is profiled by crossing a pattern or a series of patterns which emit the SEE signal and can be made ultra-thin as SEE originates from the few nanometers next to the surface. The patterns are deposited on membranes, which, in contrast with common systems like ionization chambers , are free from mechanical constraints and can then afford higher absorbed doses and be as thin as achievable. A simple demonstrator prototype has been built and successfully operated with a proton beam at the ARRONAX cyclotron at St Herblain in a wide range of currents (100 fA to 10 nA) and several energies (30 - 68 MeV). Beam profiling results from these tests are presented, and our plans for the next prototypes are mentioned.

Published
2018
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