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In view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized. This led to an architecture that is comparable to that of other commercially available bifunctional copper(ii) chelators such as p-SCN-Bn-DOTA already used in clinical trials for 64Cu-immuno-PET imaging. The C-functionalization of TE1PA on one carbon atom in the β-N position of the cyclam backbone was successfully achieved by adapting our patented methodology to the huge challenge, allowing the regiospecific mono-N-functionalization of the unsymmetrical ligand. The obtained ligand p-SCN-Bn-TE1PA was coupled to a 9E7.4 murine antibody (mAb), an IgG2a anti CD-138 for multiple myeloma (MM) targeting. The conjugation efficiency was assessed by looking at the 64Cu radiolabeling and the radiopharmaceutical 64Cu-9E7.4-p-SCN-Bn-TE1PA immunoreactivity, and in particular by comparing with 9E7.4-p-SCN-Bn-NOTA and 9E7.4-p-SCN-Bn-DOTA obtained from commercial and presumably highly efficient chelators NOTA and DOTA, respectively. The results are quite clear, showing that p-SCN-Bn-TE1PA has a coupling rate 5 times higher and an immunoreactivity 1.5 to 2 times greater than those of its two competitors. p-SCN-Bn-TE1PA also outperforms TE1PA conjugated via its carboxylic function on the same antibody. The first 64Cu-immuno-PET preclinical study in a syngeneic model of MM was performed, confirming the good in vivo properties of 64Cu-9E7.4-p-SCN-Bn-TE1PA for PET imaging, considering the high clearance even after 24 h and the particularly important tumor-to-liver ratio that was increasing at 48 h.

International audience; In view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized. This led to an architecture that is comparable to that of other commercially available bifunctional copper(ii) chelators such as p-SCN-Bn-DOTA already used in clinical trials for 64Cu-immuno-PET imaging. The C-functionalization of TE1PA on one carbon atom in the β-N position of the cyclam backbone was successfully achieved by adapting our patented methodology to the huge challenge, allowing the regiospecific mono-N-functionalization of the unsymmetrical ligand. The obtained ligand p-SCN-Bn-TE1PA was coupled to a 9E7.4 murine antibody (mAb), an IgG2a anti CD-138 for multiple myeloma (MM) targeting. The conjugation efficiency was assessed by looking at the 64Cu radiolabeling and the radiopharmaceutical 64Cu-9E7.4-p-SCN-Bn-TE1PA immunoreactivity, and in particular by comparing with 9E7.4-p-SCN-Bn-NOTA and 9E7.4-p-SCN-Bn-DOTA obtained from commercial and presumably highly efficient chelators NOTA and DOTA, respectively. The results are quite clear, showing that p-SCN-Bn-TE1PA has a coupling rate 5 times higher and an immunoreactivity 1.5 to 2 times greater than those of its two competitors. p-SCN-Bn-TE1PA also outperforms TE1PA conjugated via its carboxylic function on the same antibody. The first 64Cu-immuno-PET preclinical study in a syngeneic model of MM was performed, confirming the good in vivo properties of 64Cu-9E7.4-p-SCN-Bn-TE1PA for PET imaging, considering the high clearance even after 24 h and the particularly important tumor-to-liver ratio that was increasing at 48 h.

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The short-range (few μm in water) of the α-emitting from the spent fuel involves that the radiolytic corrosion of this kind of sample occurs at the solid/solution interface. In order to establish the role of localization of H 2 O 2 species produced by the He 2+ particle beam in water from the surface, we perform UO 2 radiolytic corrosion experiment with different distance between H 2 O 2 production area and UO 2 surface. Then, in this work, the radiolytic corrosion of UO 2 particles by oxidative species produced by 4 He 2+ radiolysis of water was investigated in open to air atmosphere. The dose rate, the localization of H 2 O 2 produced by water radiolysis and the grain boundaries present on the surface of the particles were investigated. UO 2 corrosion was investigated by in situ (during irradiation) characterization of the solid surface, analysis of H 2 O 2 produced by water radiolysis and quantification of the uranium species released into the solution during irradiation. Characterization of the UO 2 particles, surface and volume, was realized by Raman spectroscopy. UV–vis spectrophotometry was used to monitor H 2 O 2 produced by water radiolysis and in parallel the soluble uranium species released into the solution were quantified by inductively coupled plasma mass spectrometry. During the He 2+ irradiation of ultra-pure water in contact with the UO 2 particles, metastudtite phase was formed on the solid surface indicating an oxidation process of the particles by the oxidative species produced by water radiolysis. This oxidation occurred essentially on the grain boundaries and was accompanied by migration of soluble uranium species (U(VI)) into the irradiated solution. Closer to the surface the localization of H 2 O 2 formation, higher the UO 2 oxidation process occurs, whereas the dose rate had no effect on it. Simultaneously, closer to the surface the localization of H 2 O 2 formation lower the H 2 O 2 concentration measured in solution. Moreover, the metastudtite was the only secondary phase formed whatever the irradiation conditions. One hypothesis proposed in this work is the H 2 O 2 may undergo a dismutation reaction leading to the formation of OH at the UO 2 surface.

International audience; The ARRONAX cyclotron is able to deliver alpha particles at 68 MeV. In the frame of radiological research, a new method is studied to infer in situ the deposited dose: it is based on the online measurement of the bremsstrahlung (>1 keV) produced by the interaction of the incident particle with the medium. Experiments are made using bombarded poly(methyl methacrylate) (PMMA)-equivalent water targets in order to characterise this continuous X-ray spectrum. The intensity of the bremsstrahlung spectrum allows for the beam monitoring. A simulation code of the bremsstrahlung has been built, and a good agreement is found with the experimental spectra. With this simulation, it is possible to predict the sensibility of this method: it varies with the target thickness, showing a good sensibility for thin target (

Innovative accelerator-based production routes for 99Mo (and 99mTc) have been studied, comparing the 100Mo(p,x)99Mo,99mTc and 96Zr(α,n)99Mo reactions, for which a new set of measurement has been made. Theoretical and experimental cross sections have been analysed and used to calculate 99Mo production yields and specific activity (SA), considering fully enriched and commercially available target materials. Results show that the low SA resulting from the p-based route forces the use of alternative generator systems, while the α-based reaction provides very high SA 99Mo but much lower yield. Benefits and drawbacks of direct 99mTc production via the 100Mo(p,2p) reaction are also discussed.

International audience; High energy PIXE is a useful and non-destructive tool to characterize multi-layer thick samples such as cultural heritage objects. In a previous work, we demonstrated the possibility to perform quantitative analysis of simple multi-layer samples using high energy PIXE, without any assumption on their composition. In this work an in-depth study of the parameters involved in the method previously published is proposed. Its extension to more complex samples with a repeated layer is also presented. Experiments have been performed at the ARRONAX cyclotron using 68 MeV protons. The thicknesses and sequences of a multi-layer sample including two different layers of the same element have been determined. Performances and limits of this method are presented and discussed.

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The cross sections of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to a low-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%) was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga. Nuclear cross sections were measured in the energy range 35–70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu, 68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the software TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.

s of Annual Congress of the European Association of Nuclear Medicine October 13 – 17, 2018 Düsseldorf, Germany; International audience; Aim: Multiple myeloma is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow. In spite of a very active search for new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) is a new cancer treatment modality with tumour specific antibodies coupled to alpha particle-emitting radionuclides. CD138 (Syndecan-1) is found mainly in epithelial cells, but was shown to be expressed by most myeloma cells, both in human and in the mouse. The aim of the study was to evaluate the biodistribution, toxicity and efficacy of a rat Astatin-211-labelled anti-mouse CD138 antibody (211At-9E7.4) in a syngeneic mouse myeloma model. Materials and methods: C57BL/KaLwRij mice were grafted with 106 5T33 cells (murine myeloma cell line). Biodistribution was studied 15 min, 1h, 4h, 7h, 14h and 21h post-administration of 211At- 9E7.4 mAb. Toxicity (animal weight, blood cell counts and transaminase) and RIT efficacy were studied after a dose escalation using 370, 555, 740 and 1110 kBq of 211At-9E7.4 and two control groups 211At-IgG2a isotype control at 555 kBq or no treatment, 10 days after tumour engraftment. Results: Studies demonstrated a highly statistical survival benefit for the mice treated with 211At-9E7.4 at 555 kBq (p=0,0006) and 740 kBq (p

International audience; This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality.

Samples of calcite have been irradiated using both the 60.7 MeV helium ion beam of the ARRONAX (Nantes, France) cyclotron and 661.7 keV gamma radiations. The irradiation of calcite pellets results mainly in radiolytically generated gas (H2, CO2). The presence of superficial water during the calcite irradiation in a humid atmosphere is a key factor for the production of radiolysis gases. Besides, the irradiation of calcite–water biphasic media was performed. The gas released after these irradiations is quantified. No significant amount of CO2 has been detected, whereas carbonate ions act as OH• scavengers, thus inducing an increase of H2 production. The amount of hydrogen peroxide created confirms this scavenging mechanism. Finally, ionic chromatography experiments with irradiated solutions allow us to quantify the organic anions (formate HCOO–, acetate CH3COO–, propionate CH3-CH2COO–, and oxalate C2O42–) formed by calcite and/or carbonate ion radiolysis and study the variation of calcium carbonate solubil...

Introduction 226 Th ( T 1/2 =31min) is a promising therapeutic radionuclide since results, published in 2009, showed that it induces leukemia cells death and activates apoptosis pathways with higher efficiencies than 213 Bi. 226 Th can be obtained via the 230 U α decay. This study focuses on the 230 U production using the 232 Th(d,4n) 230 Pa( β −) 230 U reaction. Methods Experimental cross sections for deuteron-induced reactions on 232 Th were measured from 30 down to 19MeV using the stacked-foil technique with beams provided by the ARRONAX cyclotron. After irradiation, all foils (targets as well as monitors) were measured using a high-purity germanium detector. Results Our new 230 Pa cross-section values, as well as those of 232 Pa and 233 Pa contaminants created during the irradiation, were compared with previous measurements and with results given by the TALYS code. Experimentally, same trends were observed with slight differences in orders of magnitude mainly due to the nuclear data change. Improvements are ongoing about the TALYS code to better reproduce the data for deuteron-induced reactions on 232 Th. Conclusions Using our cross-section data points from the 232 Th(d,4n) 230 Pa reaction, we have calculated the thick-target yield of 230 U, in Bq/μA·h. This value allows now to a full comparison between the different production routes, showing that the proton routes must be preferred.

Ionizing radiation’s effects onto water molecules lead to the ionization and/or the excitation of them. Then, these phenomena are followed by the formation of radicals and molecular products. The linear energy transfer (LET), which defines the energy deposition density along the radiation length, is different according to the nature of ionizing particles. Thus, the values of radiolytic yields, defined as the number of radical and molecular products formed or consumed by unit of deposited energy, evolve according to this parameter. This work consists in following the evolution of radiolytic yield of molecular hydrogen and ferric ions according to the “Track-Segment” LET of ionizing particles (protons, helions). Concerning G(Fe3+) values, it seems that the energy deposited into the Bragg peak does not play the main role for the Fe3+ radiolytic formation, whereas for the G(H2) it is the case with a component around 40% of the Bragg peak in the dihydrogen production. Therefore, as main results of this work, for high energetic Helion and Proton beams, the G(Fe3+) values, which can be used for further dosimetry studies for example during the α radiolysis experiments, and the primary g(H2) values for the Track-Segment LET, which can be used to determine the dihydrogen production by α-emitters, are published.

International audience; The aim of this article is to give the status of nuclear data collected in the framework of the production of innovative radionuclides for therapy and diagnosis applications in collaboration with the GIP ARRONAX, which possesses a multi-particle high energy cyclotron, and to show constrains that can be put on nuclear codes. In order to assess the cross section of a given production route, experiments have been carried out using the stacked-foil technique and gamma-spectroscopy for a set of radionuclides of medical interest: photon (Tc-99m) and positon (Sc-44g) emitters for diagnosis, electron (Re-186g, Tb-155, Sn-117m) and alpha particle (Th-226, Ra-233, Bi-213) emitters for therapeutic applications. A systematic comparison has been performed between the results from the TALYS code (version 1.6) and the large set of data collected using different projectiles (proton, deuteron and alpha particle) from few MeV up to 70 MeV and covering a wide range of target masses. A better overall agreement with our experimental data has been obtained with a combination of models already included in the TALYS code differing from the default one.

International audience; Studies have been devoted to the production of alpha emitters for medical application in collaboration with the GIP ARRONAX that possesses a high energy and high intensity multi-particle cyclotron. The productions of Ra-223, Ac-225 and U-230 have been investigated from the Th-232(p,x) and Th-232(d,x) reactions using the stacked-foils method and gamma spectrometry measurements. These reactions have led to the production of several fission products, including some with a medical interest like Mo-99, Cd-115g and I-131. This article presents cross section data of fission products obtained from these undedicated experiments. These data have been also compared with the TALYS code results.

A new facility, named CERN-MEDICIS, is under construction at CERN to produce radionuclides for medical applications. In parallel, the MEDICIS-PROMED, a Marie Sklodowska-Curie innovative training network of the Horizon 2020 European Commission‘s program, is being coordinated by CERN to train young scientists on the production and use of innovative radionuclides and develop a network of experts within Europe. One program within MEDICIS-PROMED is to determine the feasibility of producing innovative radioisotopes for theranostics using a commercial middle-sized high-current cyclotron and the mass separation technology developed at CERN-MEDICIS. This will allow the production of high specific activity radioisotopes not achievable with the common post-processing by chemical separation. Radioisotopes of scandium, copper, arsenic and terbium have been identified. Preliminary studies of activation yield and irradiation parameters optimization for the production of Tb-149 will be described.

New excitation functions for proton induced nuclear reactions on natural titanium, nickel and copper were measured, using the stacked-foil technique and gamma spectrometry, up to 70 MeV. The experimental cross sections were measured using the Ti-nat(p,x) V-48, Ni-nat(p,x) Ni-57 and Cu-nat(p,x) Zn-62,Co-56 monitor reactions recommended by the International Atomic Energy Agency (IAEA), depending on the investigated energy range. Data have been extracted for the Ti-nat(p,x) Sc-43,44m,46,47,48, V-48, K-42,43, Ni-nat(p,x) Ni-56,57, Co-55,56,57,58, Mn-52,54, Cu-nat(p,x) Cu-61,64, Ni-57, Co-56,57,58,60, Zn-62,65, Mn-54 reactions. Our results are discussed and compared to the existing ones as well as with the TALYS code version 1.6 calculations using default models. Our experimental data are in overall good agreement with the literature. TALYS is able to reproduce, in most cases, the experimental trend. Our new experimental results allow to expand our knowledge on these excitation functions, to confirm the existing trends and to give additional values on a large energy range. This work is in line with the new Coordinated Research Project (CRP) launched by the IAEA to expand the database of monitor reactions.

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International audience; HIGHLIGHTS • The medical interest of terbium-155. • Deuteron induced reactions on natural gadolinium up to 34 MeV. • Excitation functions measured with the stacked-foil technique. • Comparison with the TALYS code version 1.6. • Tb-155 achievable yield and radionuclide purity. ABSTRACT Several terbium isotopes are suited for diagnosis or therapy in nuclear medicine. Tb-155 is of interest for SPECT imaging and/or Auger therapy. High radionuclide purity is mandatory for many applications in medicine. The quantification of the activity of the produced contaminants is therefore as important as that of the radionuclide of interest. The experiments performed at the ARRONAX cyclotron (Nantes, France), using the deuteron beam delivered up to 34 MeV, provide an additional measurement of the excitation function of the Gd-nat(d,x)Tb-155 reaction and of the produced terbium and gadolinium contaminants. In this study, we investigate the achievable yield for each radionuclide produced in natural gadolinium as a function of the deuteron energy. Other reactions are discussed in order to define the production route that could provide Tb-155 with a high yield and a high

International audience; Tin-117m is an interesting radionuclide for both diagnosis and therapy, thanks to the gamma-ray and electron emissions, respectively, resulting from its decay to tin-117g. The high specific activity of tin-117 m is required in many medical applications, and it can be obtained using a high energy alpha particle beam and a cadmium target. The experiments performed at the ARRONAX cyclotron (Nantes, France) using an alpha particle beam delivered at 67.4 MeV provide a measurement of the excitation function of the Cd-nat(α,x)Sn-117 m reaction and the produced contaminants. The Cd-116(α,3n)Sn-117m production cross section has been deduced from these experimental results using natural cadmium. Both production yield and specific activity as a function of the projectile energy have been calculated. These informations help to optimize the irradiation conditions to produce tin-117 m with the required specific activity using α particles with a cadmium target.

Inelastic neutron scattering for (12)C, (58)Fe, (89)Y and (208)Pb have been measured at 96 MeV at the The Svedberg Laboratory in Uppsala and double-differential cross sections are reported. Data cover an excitation energy range of 0-45 MeV and the angular intervals are 28 - 58 degrees for (12)C, 26 - 65 degrees for (58)Fe and 26 - 52 degrees for (89)Y and (208)Pb. In this experiment, neutron detection is based on conversion to protons in an active scintillator converter. An analysis technique in which the neutron spectra have been obtained through a folding procedure using the response of the detector system has been used. The results are compared to and are in reasonable agreement with several model predictions and with inelastic neutron scattering data at 65 MeV from University of California, Davis, USA.

Copper-64 has found many applications in positron emission tomography (PET). Its half-life allows to use it for dosimetric studies associated to copper-67 targeted radiotherapy in cancer treatment. The use of 64Ni(p,n)64Cu nuclear reaction is known to produce 64Cu in large amount and with a high specific activity. In this study, targets were obtained by electroplating onto a gold backing and a typical target irradiation uses 200ߙnA, 17ߙMeV protons during 30ߙmin. After irradiation, pure copper-64 is obtained using only one chromatographic column. Nickel-64 is removed in a first elution step and cobalt isotopes in a second one. The extraction yield for copper-64 is 9±23% and nickel and cobalt impurities are under the detection limit. A recovery process of nickel-64 has also been developed.

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The aim of this study is using He2+ (E=64.5 MeV) and γ radiolysis for initiating and controlling the oxidation/reduction mechanism of Mn in highly concentrated carbonate media (5 mol l−1). For obtaining the best experimental conditions, electrochemistry was performed firstly. Radiolysis was performed; first, reduction of Mn(VII) and second, oxidation of Mn(II), each part was performed under He2+ and γ-ray irradiation. Gγ(–Mn(VII))=1.07×10−7 mol J−1 and GHe2+(–Mn(VII))=3×10−8 mol J−1 that shows higher efficiency for γ radiolysis with dose rate 1000 times less than α one. Gγ(–Mn(VII))/GHe2+(–Mn(VII))=5.6 and Gγ(H2)/GHe2+(H2)=0.5 confirm radical mechanism for radio-oxidation/reduction. Heterogeneity of irradiation plays an important role on hydrolysis. Final product oxidation state was determined by XPS and SEM for Mn solid precipitated after the reduction and oxidation experiments.

HIGHLIGHTS • Production of Sc-44 m, Sc-44 g and contaminants. • Experimental values determined using the stacked-foil technique. • Thick-Target production Yield (TTY) calculations. • Comparison with the TALYS code version 1.6.Among the large number of radionuclides of medical interest, Sc-44 is promising for PET imaging. Either the ground-state Sc-44 g or the metastable-state Sc-44 m can be used for such applications, depending on the molecule used as vector. This study compares the production rates of both Sc-44 states, when protons or deuterons are used as projectiles on an enriched Calcium-44 target. This work presents the first set of data for the deuteron route. The results are compared with the TALYS code. The Thick-Target production Yields of Sc-44 m and Sc-44 g are calculated and compared with those for the proton route for three different scenarios: the production of Sc-44 g for conventional PET imaging, its production for the new 3 γ imaging technique developed at the SUBATECH laboratory and the production of a Sc-44 m/Sc-44 g in vivo generator for antibody labelling.

International audience; The (α+β)‐ (T64) and a‐titanium (T40) alloys are considered as good candidates materials for primary component circuit of mobile or stationary nuclear power plant owing to their advantageous combination of properties, i.e. low elasticity modulus, high resistance to impact loading, high strength, low density and low thermal expansion coefficient. 4He2+ irradiation has been performed on titanium alloys in water at the ARRONAX cyclotron (66.5MeV) up to a dose of 70kGy at room temperature. This work describes water radiolysis effects on titanium alloys by structural studies (XRD, SEM). It also shows an in situ electrochemical study of titanium alloys behaviors (under 4He2+ irradiation) with corrosion rate determination. Two different behaviors were observed, a decrease of corrosion rate for T40 (>200nm/y for 40kGy) and an increase for T64 (up to 1.2μm/y for 25kGy).

Rubidium-82 has a long story, starting in 1954. After preclinical studies in dogs showing that myocardial uptake of this radionuclide was directly proportional to myocardial blood flow, clinical studies were performed in the 80s leading to an approval in the USA in 1989. From that time thousands of patients have been tested and their results have been reported in 3 meta-analyses. Pooled patient-based sensitivity and specificity were respectively 0.91 and 0.90. By comparison with 99mTc-SPECT, 82Rb-PET had a much better diagnostic accuracy, especially in obese patients with BMI (Body Mass Index) ≥30 kg/m2 (85% versus 67% with SPECT) and in women with large breasts. A great advantage of 82Rb-PET is its capacity to accurately quantify myocardial blood flow. Quite importantly it has been recently shown that coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity. Moreover coronary flow reserve is a functional parameter particularly useful in the estimate of microvascular dysfunction such as in diabetes mellitus. Due to the very short half-life of rubidium-82, the effective dose calculated for a rest/stress test is roughly equivalent to the annual natural exposure and even less when stress-only is performed with a low activity compatible with a good image quality with the last generation 3D PET scanners. There is still some debate on the relative advantages of 82Rb-PET with regard to 99mTc-SPECT. For the last ten years, great technological advances substantially improved performances of SPECT with its accuracy getting closer to this of 82Rb/PET. Currently the main advantages of PET are its capacity to accurately quantify myocardial blood flow and to deliver a low radiation exposure.

Taking advantage of recent technical progress which has overcome some of the difficulties encountered in the 1960's in the radio detection of extensive air showers induced by ultra high energy cosmic rays (UHECR), a new experimental apparatus (CODALEMA) has been built and operated. We will present the characteristics of this device and the analysis techniques that have been developed for observing electrical transients associated with cosmic rays. We find a collection of events for which both time and arrival direction coincidences between particle and radio signals are observed. The counting rate corresponds to shower energies $\geq 5\times 10^{16}$ eV. The performance level which has been reached considerably enlarges the perspectives for studying UHECR events using radio detection., merge of astro-ph/0504240 and astro-ph/0504297 into one paper

International audience; The irradiation of a thorium target by light charged particles (protons and deuterons) leads to the production of several isotopes of medical interest. Direct nuclear reaction allows the production of Protactinium-230 which decays to Uranium-230 the mother nucleus of Thorium-226, a promising isotope for alpha radionuclide therapy. The fission of Thorium-232 produces fragments of interest like Molybdenum-99, Iodine-131 and Cadmium-115g. We focus our study on the production of these isotopes, performing new cross section measurements and calculating production yields. Our new sets of data are compared with the literature and the last version of the TALYS code.

A facility for detection of scattered neutrons in the energy interval 50 130 MeV, SCAttered Nucleon Detection AssembLy (SCANDAL), has recently been installed at the 20-180 MeV neutron beam facility of The Svedberg Laboratory, Uppsala. It is primarily intended for studies of elastic neutron scattering, but can be used for (n,p) and (n,d) reaction experiments as well. The performance of the spectrometer is illustrated in measurements of the (n,p) and (n,n) reactions on H-1 and C-12. In addition, the neutron beam facility is described in some detail. (C) 2002 Elsevier Science B.V. All rights reserved.

Motivated by the need of data on neutron-induced reactions with biologically relevant materials, e.g., carbon and oxygen, we have constructed and installed the MEDLEY detector array at the neutron ...

In the HINDAS program, nuclear data in the 20-2000 MeV range are evaluated by means of a combination of nuclear tmodels and well-selected intermediate- and high-energy experiments. A panoply of European accelerators is utilized to provide complete sets of experimental data for iron, lead and uranium over a large energy range. Nuclear model codes are being improved and validated against these new experimental data. This should result in enhanced ENDF-formatted data libraries up to 200 MeV, and cross sections for high-energy transport codes above 200 MeV. The impact of the new data libraries and high-energy models will be directly tested on some important parameters of an accelerator-driven system (ADS). Here, we report the recent progress of the various experimental and theoretical activities in HINDAS.

International audience; Experimental cross sections for deuteron induced nuclear reactions on natural titanium were measured, using the stacked-foil technique and gamma spectrometry, up to 34MeV with beams provided by the ARRONAX cyclotron. The experimental cross section values were monitored using the (nat)Ti(d,x)(48)V reaction, recommended by the IAEA. The excitation functions for (nat)Ti(d,x)(44m,46,47,48)Sc are presented and compared with the existing ones and with the TALYS 1.6 code calculations using default models. Our experimental values are in good agreement with data found in the literature. TALYS 1.6 is not able to give a good estimation of the production cross sections investigated in this work. These production cross sections of scandium isotopes fit with the new Coordinated Research Project (CRP) launched by the International Atomic Energy Agency (IAEA) to expand the database of monitor reactions.

Introduction: Due to its longer half-life, Sc-44 (T-1/2 = 3.97 h) as a positron emitter can be an interesting alternative to Ga-68 (T-1/2 = 67.71 min). It has been already proposed as a PET radionuclide for scouting bone disease and is already available as a Ti-44/Sc-44 generator. Sc-44 has an isomeric state, (SC)-S-44m (T-1/2 = 58.6 h), which can be co-produced with Sc-44 and that has been proved to be considered as an in-vivo PET generator Sc-44m/Sc-44. This work presents the production route of Sc-44m/Sc-44 generator from Ca-44(d,2n), its extraction/purification process and the evaluation of its performances. Methods: Irradiation was performed in a low activity target station using a deuteron beam of 16 MeV, which favors the number of (SC)-S-44m atoms produced simultaneously to Sc-44. Typical irradiation conditions were 60 min at 02 mu A producing 44 MBq of Sc-44 with a (SC)-S-44/(SC)-S-44m activity ratio of 50 at end of irradiation. Separations of the radionuclides were performed by means of cation exchange chromatography using a DGA (R) resin (Triskem). Then, the developed process was applied with bigger targets, and could be used for preclinical studies. Results: The extraction/purification process leads to a radionucleidic purity higher than 99.99% (Sc-43, Sc-46, Sc-48 < DL). Sc-44m/Sc-44 labeling towards DOTA moiety was performed in order to get an evaluation of the specific activities that could be reached with regard to all metallic impurities from the resulting source. Reaction parameters of radiolabeling were optimized, reaching yields over 95%, and leading to a specific activity of about 10-20 MBq/nmol for DOTA. A recycling process for the enriched Ca-44 target was developed and optimized. Conclusion: The quality of the final batch with regard to radionucleidic purity, specific activity and metal impurities allowed a right away use for further radiopharmaceutical evaluation. This radionucleidic pair of (SC)-S-44m/(SC)-S-44 offers a quite interesting PET radionuclide for being further evaluated as an in-vivo generator. (C) 2015 Elsevier Inc. All rights reserved.

Radioimmunotherapy (RIT) has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (mAbs), and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved in the treatment of B cell lymphoma: 131I-tositumomab (Bexxar®) and 90Y-ibritumomab tiuxetan (Zevalin®). RIT can be integrated in clinical practice for treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy in frontline treatment in FL patients. High-dose treatment, RIT as consolidation, RIT in first-line treatment, fractionated RIT, and use of new humanized mAbs, in particular targeting CD22, showed promising results in B cell lymphoma. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiations and less accessible to large molecules such as mAbs, clinical efficacy remains limited. However, RIT used in minimal or small-size metastatic disease has shown promising clinical efficacy. Pretargeting approaches have been potential in increasing the therapeutic index of radiolabeled antibodies. Finally, new beta emitters such as lutetium-177 with better physical properties will further improve the safety of RIT. Moreover, alpha emitters such as bismuth-213 or astatine-211 offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the setting of consolidation. Personalized dosimetry protocols, particularly based on quantitative positron emission tomography (PET) imaging, should be developed to optimize injected activity.

International audience; The high energy PIXE (HEPIXE) method is a multi-elemental non-destructive ion beam analysis technique. It is based on the detection of the X-ray emitted due to the interaction of high energy particle beam with a sample. This technique is fast and allows the analysis of heavy and medium elements in thin (lm), thick (mm) and multilayer samples. At the ARRONAX facility (Nantes, France), the HEPIXE method has been used to determine the composition of natural and synthetic sodalites. Photochromic properties of these samples are supposed to come from the trace elements (concentration in the ppm range) present in the samples. Taking advantage of the 70 MeV proton beam available at our facility, the HEPIXE methodhas been also used to study multilayer samples. It has been shown that it is possible to determine the composition of each layer, their thicknesses and their depth position by analyzing the recorded X-ray spectra.

International audience; To advance the development of a radiobiological experimental set-up for alpha particle irradiations at the Arronax cyclotron, experiments were performed to get the dose response of Gafchomic EBT2 films for alpha particles at 48.3 MeV. A system has been developed using a thin monitor copper foil and an X-ray spectrometer to measure the beam intensity and to calculate the delivered dose. On the other hand, the authors have irradiated EBT2 films, with 6-MV X rays, to get the dose response of EBT2 films for photons. The dose response curve for alpha particles shows an effect of polymerisation saturation compared with the dose response curve for photons.

International audience; Cross sections for the (d,n), (d,2n) and (d,4n) reactions on 232Th were measured using the stackedfoil technique with beams provided by the ARRONAX cyclotron. These data are of relevance for the production of radionuclides. The measured cross sections were compared with previous measurements as well as with theoretical calculations using the code TALYS.

A method is proposed for production of polonium-210 via the 209Bi(α, 3n)210At nuclear reaction. Bombardment of a bismuth-209 target was performed with a 37 MeV alpha-particle beam that leads to the production of astatine-210 (T 1/2 = 8.1 h), which decays to polonium-210. It is purified from the bismuth target matrix by employing liquid–liquid extraction using tributyl phosphate (TBP) in para-xylene from 7 M hydrochloric acid. Back extraction of polonium-210 was performed by 9 M nitric acid. This method allows to purify a tracer amount of Po-210 (2.6 · 10 –13 mol) from macroscopic amount of Bi (2.8 · 10 –2 mol).

International audience

International audience; The ARRONAX cyclotron is fully operational since the end of 2010. It delivers projectiles (p, d, alpha) at high energy (up to 70 MeV for protons) and high intensity(2*375 mu A for protons). The main fields of application of ARRONAX are radionuclide production for nuclear medicine and irradiation of inert or living materials for radiolysis and radio-biology studies. A large part of the beam time will be used to produce radionuclides for targeted radionuclide therapy (copper-67, scandium-47 and astatine-211) as well as for PET imaging (scandium-44, copper-64, strontium-82 for rubidium-82 generators, and germanium-68 for gallium-68 generators). Since June 2012, large scale production of Sr-82 has started with rubidium chloride (RbCl) targets. Several improvements are being explored which consist of changing the target material from RbCl to Rb metal and introducing an additional target behind the rubidium assembly. Thus, a target alloy of nickel/gallium for germanium-68 production has been developed. It is obtained by electroplating and exhibits a better thermal behavior than the natural gallium target used in most production facilities.

The high-specific activity 99Mo accelerator-based production, via the (α,n) reaction on 96Zr-enriched target, has been investigated in the present work. The excitation function measurement has been performed in the energy range 8–34 MeV at the ARRONAX facility, using the well-known stacked foils technique on natural zirconium as target. A general good agreement in the cross section trend has been observed, once compared to former measurements. A different (i.e. higher) peak value and a shift of about 2 MeV towards larger energies have however been found. Assuming a fully enriched 96Zr target irradiated by an α-beam at suitable energy (E = 25 MeV), the 99Mo production yield has thus been estimated. At last the alternative production routes, based on the 96Zr(α,n)99Mo and 100Mo(p,x)99Mo/99mTc reactions, are compared.

A model allowing to simulate the production of clusters is developed and applied to heavy-ion reactions at intermediate energies. The model investigates the geometrical properties of the dynamically generated one-body phase space. The collision process is entirely governed by the Landau-Vlasov model, which provides the time evolution of the one-body phase-space distribution. Particles emitted during successive time intervals of the dynamics are gathered together into subensembles to which a clusterization procedure is applied. Comparison with the experimental data for the Ar(65 MeV/nucleon) + Al reaction shows that the average behaviour of particle-dependent global observables is correctly reproduced within this framework. These results point out that the studied global properties of heavy-ion collisions greatly rely on the dynamical effects of the primary non-steady stage of the nuclear reaction.

Observations of heavy remnants emitted at forward angles with high velocities and high associated particle multiplicities have been used to select central collisions of 35A MeV {sup 63}Cu with {sup 197}Au. The data indicate that these remnants, both fission fragments and evaporation residuelike products, result from the deexcitation of nuclei with A{approximately}225{endash}240 having excitation energies of {approximately} 800{endash}1300 MeV. Similar particle multiplicities are observed for both evaporative and fission decay channels. Modeling the results with hybrid codes which treat entrance channel dynamics followed by sequential statistical decay requires the inclusion of some delay in the fission channel to produce heavy remnants with mass A{ge}130, but the trend of the predicted velocities of these heavy remnants is different from that of the experiments. Calculations with a dynamic model based on the molecular dynamics approach have also been performed and lead to similar results. He and Li isotope yield ratios and the apparent temperatures derived from those ratios are similar to those previously reported for excited nuclei in this mass region. Temperatures derived from other yield ratios are also similar once a self-consistent treatment, taking into account population and decay of known excited states, is applied. The derived temperatures show little variation more » with excitation energy, suggesting that a limiting temperature may be reached at relatively low excitation energy, although the interpretation of this result and the determination of the actual initial value of this temperature is model dependent. Comments on the application of the double isotope yield ratio technique to extraction of the nuclear caloric curve are made. {copyright} {ital 1997} {ital The American Physical Society} « less

Introduction The ARRONAX cyclotron, acronym for “Accelerator for Research in Radiochemistry and Oncology at Nantes Atlantique” is a new facility installed in Nantes, France. A dedicated program has been launched on production of innovative radioisotopes for PET imaging and for β − and α targeted radiotherapy using protons or α particles. Since the accelerator is also able to deliver deuteron beams up to 35 MeV, we have reconsidered the possibility of using them to produce medical isotopes. Indeed, in some cases, the use of deuterons allows higher production yield than protons. Methods 186Re is a β − emitter which has chemical properties close to the widely used 99mTc and has been used in clinical trials for palliation of painful bone metastases resulting from prostate and breast cancer. 186Re production cross section has been measured between 9 and 23 MeV using the ARRONAX deuteron beam and the stacked-foil technique. A novelty in our work is the use of a monitor foil behind each natW target foil in order to record efficiently the deuteron incident flux and energies all over the stack relying on the International Atomic Energy Agency (IAEA) recommended cross section of the natTi(d,x)48V reaction. Since a good optimization process is supposed to find the best compromise between production yield and purity of the final product, isotope of interest and contaminants created during irradiation are measured using gamma spectrometry. Results Our new sets of data are presented and compared with the existing ones and with results given by the TALYS code calculations. The thick target yield (TTY) has been calculated after the fit of our experimental values and compared with the IAEA recommended ones. Conclusions Presented values are in good agreement with existing data. The deuteron production route is clearly the best choice with a TTY of 7.8 MB/μAh at 30 MeV compared to 2.4 MBq/μAh for proton as projectile at the same energy. The TALYS code gives satisfactory results for 183,186Re isotopes.

Introduction Among the number of generator systems providing radionuclides with decay parameters promising for imaging and treatment applications, there is the 44 Ti (T 1/2 =60years)/ 44 Sc (T 1/2 =3.97h) generator. This generator provides a longer-lived daughter for extended PET/CT measurements compared to the chemically similar system 68 Ge/ 68 Ga. Scandium also exists as 47 Sc, a potential therapeutic radionuclide. It is possible to produce 44 Sc in a cyclotron using, for example, the 44 Ca (d, n) 44 Sc nuclear reaction. In that case, the isomeric state 44m Sc (T 1/2 =58.6h) is co-produced and may be used as an in vivo 44m Sc/ 44 Sc generator. The aim of this study is to evaluate the feasibility of this in vivo 44m Sc/ 44 Sc generator and to demonstrate that the daughter radionuclide stays inside the chelator after decay of the parent radionuclide. Indeed, the physico-chemical process occurring after the primary radioactive decay (EC, IT, Auger electron …) has prevented in many cases the use of in-viv o generator, because of the post-effect as described in the literature. Methods The DOTA macrocyclic ligand forms stable complexes with many cations and has been shown to be the most suitable chelating moiety for scandium. Initially, the radiolabeling of DOTA and a DOTA-peptide (DOTATATE) with Sc was performed and optimized as a function of time, pH, metal-to-ligand ratio and temperature. Next, the physico-chemical processes that could occur after the decay (post-effect) were studied. 44m Sc(III)-labeled DOTA-peptide was quantitatively adsorbed on a solid phase matrix through a hydrophobic interaction. Elutions were then performed at regular time intervals using a DTPA solution at various concentrations. Finally, the radiolabelled complex stability was studied in serum. Results Radiolabeling yields ranged from 90% to 99% for metal-to-ligand ratio ranging from 1:10 to 1:500 for DOTA or DOTATATE respectively. The optimum physico-chemical parameters were pH=4–6, t=20min, T=70°C. Then, the 44m Sc-DOTATATE complex, radiolabeled at 98%, was adsorbed through a hydrophobic interaction to a solid phase. Unlabeled scandium was completely eluted from the column whereas the Sc-DOTATATE complex was 100% retained. The release of 44 Sc from the complex due to decay was less than 1% over 2 periods of 44m Sc, independent of the DTPA concentration used for elution. 44m Sc/ 44 Sc-DOTATATE was stable in serum over 72h. Conclusions The results indicate that the decay of 44m Sc to 44 Sc does not affect the integrity of the radiolabeled compound. Thus the 44m Sc/ 44 Sc generator is chemically valid and stable in serum. It could be used for PET imaging as an in-vivo generator increasing the life time of the scandium and allowing the use of antibody as labelled compound. Further in-vivo biological evaluations should complete this work.

40Ar+107 Ag reactions at 27 AMeV and 44AMeV have been studied within the Landau Vlasov microscopic transport model. In this framework the main characteristics of primary partners of binary collisions are shown to be well described, and information aboutσnn can be extracted as well as the angular momentum associated with the heavy fragment. Different contributions to the total energy are studied as a function of the reaction time. Our numerical method is compared with the results obtained using experimental techniques like proton spectra. Their impact parameter and energy dependences have been studied and the estimated “temperature parameter” is in agreement with the experimental results.