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Saint-Sauveur-en-Rue, France

Haddad F.,Ecole des Mines de Nantes | Barbet J.,University of Nantes | Chatal J.-F.,GIP Arronax
Current Radiopharmaceuticals | Year: 2011

A new high-energy and high-intensity cyclotron, ARRONAX, has been set into operation in 2010. ARRONAX can accelerate both negative ions (H - and D -) and positive ions (He ++ and HH +). Protons can be accelerated from 30 MeV up to 70 MeV with a maximum beam intensity of 2 × 375 μAe whereas He ++ can be accelerated at 68 MeV with a maximum beam current of 70 μAe. The main fields of application of ARRONAX are radionuclide production for nuclear medicine and irradiation of inert or living materials for radiolysis and radiobiology 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 the beginning of the project a particular interest has been devoted to alpha-radionuclide therapy using complex ligands like antibodies and astatine-211 has been selected as a radionuclide of choice for such type of applications. Associated with appropriate carriers, all these radionuclides will respond to a maximum of unmet clinical needs. © 2011 Bentham Science Publishers Ltd. Source


Kraeber-Bodere F.,University of Nantes | Kraeber-Bodere F.,Institute Of Cancerologie Of Louest Rene Gauducheau | Rousseau C.,Institute Of Cancerologie Of Louest Rene Gauducheau | Rousseau C.,University of Nantes | And 10 more authors.
Frontiers in Pharmacology | Year: 2015

Labeled antibodies, as well as their fragments and antibody-derived recombinant constructs, have long been proposed as general vectors to target radionuclides to tumor lesions for imaging and therapy. They have indeed shown promise in both imaging and therapeutic applications, but they have not fulfilled the original expectations of achieving sufficient image contrast for tumor detection or sufficient radiation dose delivered to tumors for therapy. Pretargeting was originally developed for tumor immunoscintigraphy. It was assumed that directly-radiolabled antibodies could be replaced by an unlabeled immunoconjugate capable of binding both a tumor-specific antigen and a small molecular weight molecule. The small molecular weight molecule would carry the radioactive payload and would be injected after the bispecific immunoconjugate. It has been demonstrated that this approach does allow for both antibody-specific recognition and fast clearance of the radioactive molecule, thus resulting in improved tumor-to-normal tissue contrast ratios. It was subsequently shown that pretargeting also held promise for tumor therapy, translating improved tumor-to-normal tissue contrast ratios into more specific delivery of absorbed radiation doses. Many technical approaches have been proposed to implement pretargeting, and two have been extensively documented. One is based on the avidin-biotin system, and the other on bispecific antibodies binding a tumor-specific antigen and a hapten. Both have been studied in preclinical models, as well as in several clinical studies, and have shown improved targeting efficiency. This article reviews the historical and recent preclinical and clinical advances in the use of bispecific-antibody-based pretargeting for radioimmunodetection and radioimmunotherapy of cancer. The results of recent evaluation of pretargeting in PET imaging also are discussed. © 2015 Kraeber-Bodéré, Rousseau, Bodet-Milin, Frampas, Faivre-Chauvet, Rauscher, Sharkey, Goldenberg, Chatal and Barbet. Source


Guertin A.,French National Center for Scientific Research | Duchemin C.,French National Center for Scientific Research | Haddad F.,French National Center for Scientific Research | Michel N.,GIP Arronax | Metivier V.,French National Center for Scientific Research
Nuclear Medicine and Biology | Year: 2014

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 23MeV 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 7.8MB/μAh at 30MeV compared to 2.4MBq/μAh for proton as projectile at the same energy. The TALYS code gives satisfactory results for 183,186Re isotopes. © 2014 Elsevier Inc. Source


Champion J.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Sabatie-Gogova A.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Sabatie-Gogova A.,University of Nantes | Bassal F.,University of Nantes | And 5 more authors.
Journal of Physical Chemistry A | Year: 2013

This work aims to resolve some controversies about astatine(III) hydroxide species present in oxidant aqueous solution. AtO+ is the dominant species existing under oxidizing and acidic pH conditions. This is consistent with high-performance ion-exchange chromatography data showing the existence of one species holding one positive charge. A change in speciation occurs as the pH changes from 1 to 4, while remaining under oxidizing conditions. Dynamic experiments with ion-exchange resins evidence the existence of a neutral species witnessed by its elution in the void volume. Batch-experiments using a competition method show the exchange of one proton indicating the formation of the AtO(OH) species. The hydrolysis thermodynamic constant, extrapolated to zero ionic strength, was determined to be 10-1.9. This value is supported by two-component relativistic quantum calculations and therefore allows disclosing unambiguously the structure of the formed species. © 2013 American Chemical Society. Source


Bourgeois M.,University of Nantes | Rajerison H.,University of Nantes | Guerard F.,University of Nantes | Mougin-Degraef M.,University of Nantes | And 5 more authors.
Nuclear Medicine Review | Year: 2011

During the carcinogenesis process, tumour cells often have a more rapid proliferation potential than cells that participate in blood capillary formation by neoangiogenesis. As a consequence of the poorly organized vasculature of various solid tumours, a limited oxygen delivery is observed. This hypoxic mechanism frequently occurs in solid cancers and can lead to therapeutic resistance. The present selected literature review is focused on the comparison of two positron emitting radiopharmaceuticals agents, which are currently leaders in tumour hypoxia imaging by PET. [ 18F]-fluoromisonidazole (= FMISO) is most commonly used as an investigational PET agent with an investigational new drug exemption from the FDA, while [ 64Cu]- diacetyl-bis(N 4-methylthiosemicarbazone) ( 64Cu-ATSM) has been presented as an alternative radiopharmaceutical not yet readily available. The comparison of these two radiopharmaceutical agents is particularly focused on isotope properties, radiopharmaceutical labelling process, pharmacological mechanisms, dosimetry data in patients, and clinical results in terms of image contrast. PET imaging has demonstrated a good efficacy in tumour hypoxia imaging with both FMISO and Cu-ATSM, but FMISO has presented too slow an in vivo accumulation and a weak image contrast of the hypoxia area. Despite a less favourable dosimetry, 64Cu-ATSM appears superior in terms of imaging performance, calling for industrial and clinical development of this innovative radiopharmaceutical. Copyright © 2011 Via Medica. Source

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