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6 results on '"GIPARRONAX [Saint-Herblain, France]"'

1. IAEA Activities on 67Cu, 186Re, 47Sc Theranostic Radionuclides and Radiopharmaceuticals

Author

G. Pupillo, Mohamed A. Gizawy, Amir Reza Jalilian, Aruna Korde, Cyrille Alliot, Sandor Takacs, Katherine Gagnon, Joao A. Osso, Jeong H. Park, Kotaro Nagatsu, Mayeen Uddin Khandaker, Aleksander Bilewicz, Suzanne E. Lapi, Sudipta Chakarborty, Subhani Okarvi, Mohammad R.A. Rovais, Valeriia N. Starovoitova, Renata Mikolajczak, Abdul Hamid Al Rayyes, International Atomic Energy Agency [Vienna] (IAEA), Egyptian Atomic Energy Authority (EAEA), 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), GIPARRONAX [Saint-Herblain, France], Institute For Nuclear Research and Nuclear Energy (INRNE), Bulgarian Academy of Sciences (BAS), Bhabha Atomic Research Centre (BARC), Government of India, Department of Atomic Energy, Nuclear Science and Technology Research Institute [Tehran, Iran] (NSTRI), Istituto Nazionale di Fisica Nucleare (INFN), National Institutes for Quantum and Radiological Science and Technology (QST), Korea Atomic Energy Research Institute [Daejeon, south Korea] (KAERI), Sunway University [Malaysia], Radioisotope Centre POLATOM [Otwock, Pologne] (POLATOM), Institute of Nuclear Chemistry and Technology [Warsaw, Poland] (INCT), King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Biacore/GE Healthcare [Uppsala], Atomic Energy Commission of Syria (AECS), Gouvernement de la Syrie, University of Alabama at Birmingham [ Birmingham] (UAB), and Bernardo, Elizabeth

Subjects
Pharmacology, Engineering, medicine.medical_specialty, 186Re, business.industry, theranostic, Member states, IAEA, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, research reactor, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, 47Sc, 67Cu, medicine, cyclotron, Radiology, Nuclear Medicine and imaging, Medical physics, CRP, business
Abstract

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on the request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview.

Published
2021

2. Copper-64-Labeled 1C1m-Fc, a New Tool for TEM-1 PET Imaging and Prediction of Lutetium-177-Labeled 1C1m-Fc Therapy Efficacy and Safety

Author

John O. Prior, Silvano Gnesin, Séverine Marionneau-Lambot, Jacques Barbet, David Viertl, Niklaus Schaefer, Judith Anna Delage, Steven M. Dunn, Mickaël Bourgeois, Julie K. Fierle, Sébastien Gouard, Michel Chérel, Patricia Le Saëc, Alain Faivre-Chauvet, Université de Lausanne = University of Lausanne (UNIL), GIPARRONAX [Saint-Herblain, France], 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Siric ILIADDHU Oncogreffe, ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), CHEREL, Michel, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, and NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID

Subjects
Cancer Research, Biodistribution, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, theranostic, Uterus, PET imaging, DOTA conjugation, Lutetium-177, copper-64, dosimetry, tumor endothelial marker 1, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neuroblastoma, medicine, DOTA, Dosimetry, RC254-282, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, medicine.anatomical_structure, Oncology, chemistry, Cancer cell, Copper-64, Nuclear medicine, business, Conjugate
Abstract

Simple Summary The prevalence of TEM-1 in the vasculature and the stroma of solid tumors and in malignant cells of sarcomas suggests that targeting TEM-1 could have therapeutic benefit. In this context, an anti-TEM-1 companion diagnostic may assist in the personalized medicine approach, whereby TEM-1 expression is exploited as a biomarker to select patients that would most benefit from a treatment directed toward the TEM-1 antigen. In our previous works, we have selected 1C1m-Fc, a fusion protein antibody, radiolabeled it with 177Lu and demonstrated that [177Lu]Lu-1C1m-Fc has interesting therapeutic performance. To define a suitable radiopharmaceutical companion for theranostic applications, 64Cu was chosen to radiolabel the fusion protein antibody. The aim of this work was thus to determine if [64Cu]Cu-1C1m-Fc can be considered for TEM-1 PET imaging and to predict the dosimetry of the [177Lu]Lu-1C1m-Fc companion therapy. Abstract 1C1m-Fc, a promising anti-TEM-1 DOTA conjugate, was labeled with 64Cu to target cancer cells for PET imaging and predicting the efficacy and safety of a previously studied [177Lu]Lu-1C1m-Fc companion therapy. DOTA-conjugated 1C1m-Fc was characterized by mass spectrometry, thin layer chromatography and immunoreactivity assessment. PET/CT and biodistribution studies were performed in human neuroblastoma xenografted mice. Absorbed doses were assessed from biodistribution results and extrapolated to 177Lu based on the [64Cu]Cu-1C1m-Fc data. The immunoreactivity was ≥ 70% after 48 h of incubation in serum, and the specificity of [64Cu]Cu-1C1m-Fc for the target was validated. High-resolution PET/CT images were obtained, with the best tumor-to-organ ratios reached at 24 or 48 h and correlated with results of the biodistribution study. Healthy organs receiving the highest doses were the liver, the kidneys and the uterus. [64Cu]Cu-1C1m-Fc could be of interest to give an indication of 177Lu dosimetry for parenchymal organs. In the uterus and the tumor, characterized by specific TEM-1 expression, the 177Lu-extrapolated absorbed doses are overestimated because of the lack of later measurement time points. Nevertheless, 1C1m-Fc radiolabeled with 64Cu for imaging would appear as an interesting radionuclide companion for therapeutic application with [177Lu]Lu-1C1m-Fc.

Published
2021

3. Radiolabeling Chemistry with Heavy Halogens Iodine and Astatine

Author

Jean-François Gestin, Cyrille Alliot, Romain Eychenne, François Guérard, GIPARRONAX [Saint-Herblain, France], 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), 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), and Bernardo, Elizabeth

Subjects
010405 organic chemistry, Radiochemistry, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, protein labeling, stability, Iodine, bioconjugates, 01 natural sciences, 3. Good health, 030218 nuclear medicine & medical imaging, 0104 chemical sciences, radioiodine, 03 medical and health sciences, 0302 clinical medicine, radiohalogenation, chemistry, [SDV.CAN] Life Sciences [q-bio]/Cancer, Halogen, astatine, Astatine
Abstract

International audience; Iodine and astatine radioisotopes are particularly attractive in nuclear medicine since their available isotopes cover all imaging and therapeutic modalities, from SPECT and PET imaging to beta, alpha and Auger electron therapy. Furthermore, their radiolabeling chemistry is highly versatile, being mainly based on covalent chemistry, unlike most other radionuclides that are metals. This makes them easily adaptable for the radiolabeling of a broad range of carrier compounds, from small molecules to large proteins. Iodine and astatine being both neighboring halogens, their radiolabeling chemistry is very similar. Knowledge on At is however limited given its low availability over the past decades and the facts that it exists only as short-lived isotopes, which has long hampered the study of its chemical properties. Nonetheless, recent research has highlighted features that distinguish it from its lighter halogen homologues and late developments open new perspectives with astatine radioisotopes to produce radiopharmaceuticals.In this chapter, the basics of iodine and astatine labeling chemistry are covered in parallel, starting with general principles and then detailing more specific applications and issue. In a first part the main production methods for the most relevant radionuclides, and the corresponding chemicals forms available for radiolabeling chemistry are presented. Radiolabeling reactions, which can be classified as electrophilic or nucleophilic, are introduced and their advantages and drawbacks are discussed. The second part introduces issues encountered in the specific case of proteins radiolabeling and the main strategies available. Finally, a third part discusses the stability issues encountered with iodine and especially At-labeled radiopharmaceuticals and the main approaches under investigation to improve it. The perspectives sections discuss the potential of iodine and astatine radioisotopes in the context of the development of the radiotheranostic modality.

Published
2021

4. Anti-tumor efficacy of a combination therapy with PD-L1 targeted alpha therapy and adoptive cell transfer of PD-1 deficient melanoma-specific human T-lymphocytes

Author

Marotte, L, Capitao, M, Deleine, C, Beauvais, T, Cadiou, G, Perrin, J, Chérel, M, Scotet, E, Guilloux, Y, Bruchertseifer, F, Morgenstern, A, Jarry, A, Gaschet, J, Labarrière, Nathalie, Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), 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), LabEX IGO Immunothérapie Grand Ouest, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre hospitalier universitaire de Nantes (CHU Nantes), GIPARRONAX [Saint-Herblain, France], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), European Commission - Joint Research Centre [Karlsruhe] (JRC), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), 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), Nantes Université (Nantes Univ), and LABARRIERE, Nathalie

Subjects
targeted alpha therapy, gene editing, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, RC581-607, [SDV.CAN] Life Sciences [q-bio]/Cancer, pd-l1, PD-1, melanoma, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Immunologic diseases. Allergy, RC254-282, adoptive cell transfer
Abstract

International audience; The optimization of adoptive transfer approaches of anti-tumor T cells requires both the functional improvement of the injected T cells and the modulation of the tumor microenvironment, favoring the recruitment of these T cells and their activation. We have recently shown the therapeutic benefit of two approaches tested individually in a melanoma model wich were on one hand the adoptive transfer of specific T cells deficient for the expression of the inhibitory receptor PD-1, and on the other hand PD-L1 targeted alpha therapy (TAT). In this study, we sought to investigate the efficacy of these two therapies combined, compared to each monotherapy, in order to evaluate the synergy between these two approaches, in the same melanoma model. Here we used melanoma-specific T-cell clones, previously validated for the edition of PDCD1 gene and with previously demonstrated superior anti-tumor activity than their wild-type counterparts, after adoptive transfer in NSG mice engrafted with PD-L1 expressing human melanoma tumors. We also used a previously validated TAT approach, using a 213Bi-anti-human- PD-L1 mAb, alone or in combination with adoptive cell transfer, in the same mouse model. We confirmed previous results obtained with each monotherapy and documented the safety and the superior ability of a combination between the adoptive transfer of PD-1 deficient T cells and TAT targeting PD-L1 to control the growth of melanoma tumors in NSG mice. This study provides the first proof-of-concept of the efficacy of a combination therapy using TAT, adoptive cell transfer and genomic editing of IC-coding genes.

Published
2021

5. 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

6. Prospects for Enhancing Efficacy of Radioimmunotherapy

Author

Jean-François Chatal, Clément Bailly, François Guérard, Caroline Bodet-Milin, Caroline Rousseau, Françoise Kraeber-Bodéré, Michel Chérel, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, GIPARRONAX [Saint-Herblain, France], and Bernardo, Elizabeth

Subjects
Oncology, medicine.medical_specialty, Hematology, business.industry, medicine.medical_treatment, Alpha (ethology), [SDV.CAN]Life Sciences [q-bio]/Cancer, Radioimmunotherapy, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Theranostic, Alpha-RIT, 030220 oncology & carcinogenesis, Internal medicine, medicine, Fractionation, Therapy efficacy, business, Pretargeting
Abstract

International audience; Radioimmunotherapy has been in use for more than 20 years and has progressed significantly since its efficacy has first been demonstrated in hematology. Yet it still has limitations that prevent its large-scale clinical use. This chapter reviews recent developments to overcome these limitations including new antibody specifici-ties, pretargeting methods, fractionated injections, and the use of alpha emitters. Immuno-PET is also likely to assist in selecting patients for radioimmunotherapy, optimizing injected activities, and noninvasively monitoring therapy efficacy.

Published
2018

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