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1. Antitumor Immunity Induced after α Irradiation

Author

Gorin, Jean-Baptiste, Ménager, Jérémie, Gouard, Sébastien, Maurel, Catherine, Guilloux, Yannick, Faivre-Chauvet, Alain, Morgenstern, Alfred, Bruchertseifer, Frank, Chérel, Michel, Davodeau, François, and Gaschet, Joëlle

Published
2014
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6. Targeted-Alpha-Therapy Combining Astatine-211 and anti-CD138 Antibody in a Preclinical Syngeneic Mouse Model of Multiple Myeloma Minimal Residual Disease

Author

Gouard, Sébastien, primary, Maurel, Catherine, additional, Marionneau-Lambot, Séverine, additional, Dansette, Delphine, additional, Bailly, Clément, additional, Guérard, François, additional, Chouin, Nicolas, additional, Haddad, Ferid, additional, Alliot, Cyril, additional, Gaschet, Joëlle, additional, Eychenne, Romain, additional, Kraeber-Bodéré, Françoise, additional, and Chérel, Michel, additional

Published
2020
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8. SPECT-CT Imaging of Dog Spontaneous Diffuse Large B-Cell Lymphoma Targeting CD22 for the Implementation of a Relevant Preclinical Model for Human

Author

Etienne, Floriane, Berthaud, Maxime, Nguyen, Frédérique, Bernardeau, Karine, Maurel, Catherine, Bodet-Milin, Caroline, Diab, Maya, Abadie, Jérôme, Gouilleux-Gruart, Valérie, Vidal, Aurélien, Bourgeois, Mickael, Chouin, Nicolas, Ibisch, Catherine, Davodeau, François, Oncologie nucléaire (CRCINA - Département NOHMAD - Equipe 13), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-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 - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-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 - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Animaux Modèles pour la Recherche en Oncologie [Nantes] (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Stress Adaptation and Tumor Escape in breast cancer - SATE (CRCINA - Département ONCO - Equipe 8), Plateforme 'Production de protéines recombinantes' (P2R - INSERM UMS016/CNRS UMS3556/UN FED4203), 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 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), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Cyclotron ARRONAX [Saint-Herblain], ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), This work was supported by the Institut Thématique MultiOrganismes (ITMO) Cancer of the Alliance pour les sciences de la vie et de la santé (AVIESAN) jointly with the Institut National du Cancer (INCA) under one grant entitled: Spontaneous tumor models in animals for translational research in oncology no. A11196NS (CANIMAB). Financial support was also provided by a Physics, Mathematics and Engineering sciences applied to the Cancer Research grant (DogPPK project) awarded by INSERM and INCa., 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), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Université de Tours (UT), 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), 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
comparative oncology, diffuse large B-cell lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, SPECT-CT imaging, internalization, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, immune system diseases, monoclonal antibody, hemic and lymphatic diseases, dog, internalization Etienne et al Radiolabeled Anti-canine CD22 Antibodies, CD22, Original Research
Abstract

International audience; Antibodies directed against CD22 have been used in radioimmunotherapy (RIT) clinical trials to treat patients with diffuse large B-cell lymphoma (DLBCL) with promising results. However, relevant preclinical models are needed to facilitate the evaluation and optimization of new protocols. Spontaneous DLBCL in dogs is a tumor model that may help accelerate the development of new methodologies and therapeutic strategies for RIT targeting CD22. Seven murine monoclonal antibodies specific for canine CD22 were produced by the hybridoma method and characterized. The antibodies' affinity and epitopic maps, their internalization capability and usefulness for diagnosis in immunohistochemistry were determined. Biodistribution and PET imaging on a mouse xenogeneic model of dog DLBCL was used to choose the most promising antibody for our purposes. PET-CT results confirmed biodistribution study observations and allowed tumor localization. The selected antibody, 10C6, was successfully used on a dog with spontaneous DLBCL for SPECT-CT imaging in the context of disease staging, validating its efficacy for diagnosis and the feasibility of future RIT assays. This first attempt at phenotypic imaging on dogs paves the way to implementing quantitative imaging methodologies that would be transposable to humans in a theranostic approach. Taking into account the feedback of existing human radioimmunotherapy clinical trials targeting CD22, animal trials are planned to investigate protocol improvements that are difficult to consider in humans due to ethical concerns.

Published
2020
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9. Optimization of Dosimetry in Alpha Therapy: Microlocalisation of 223Ra in Mouse Models of Metastasis from Prostate Cancer and Renal Cell Carcinoma

Author

Benabdallah, Nadia, primary, Sai-Maurel, Catherine, additional, Franck, Didier, additional, de Labriolle-Vaylet, Claire, additional, Desbrée, Aurélie, additional, Cherel, Michel, additional, Gouard, Sébastien, additional, Bertho, Jean-Marc, additional, Kereselidze, Dimitri, additional, Donnard, Jérôme, additional, Lerondel, Stéphanie, additional, Chauchereau, Anne, additional, Chouin, Nicolas, additional, and Bernardini, Michela, additional

Published
2019
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10. TE1PA as Innovating Chelator for 64Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model

Author

Navarro, Anne-Sophie, primary, Le Bihan, Thomas, additional, Le Saëc, Patricia, additional, Bris, Nathalie Le, additional, Bailly, Clément, additional, Saï-Maurel, Catherine, additional, Bourgeois, Mickaël, additional, Chérel, Michel, additional, Tripier, Raphaël, additional, and Faivre-Chauvet, Alain, additional

Published
2019
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11. Sensitivity of pretargeted immunoPET using 68 Ga-peptide to detect colonic carcinoma liver metastases in a murine xenograft model: Comparison with 18 FDG PET-CT

Author

Foubert, Fanny, Gouard, Sebastien, Sai-Maurel, Catherine, Cherel, Michel, Faivre-Chauvet, Alain, Goldenberg, David, Barbet, Jacques, Bailly, Clément, Bodet-Milin, Caroline, Carlier, Thomas, Kraeber-Bodéré, Françoise, Touchefeu, Yann, Frampas, Eric, 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), Département d'hépato-gastro-entérologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut des Maladies de l’Appareil Digestif [CHU Nantes], Département de Médecine Nucléaire [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), IBC Pharmaceuticals Inc [Morris Plains, NJ, USA], Immunomedics Inc. [Morris Plains, NJ, USA], GIP ARRONAX [Nantes] (Saint-Herblain), Université de Nantes (UN), Département de Radiologie [CHU Nantes], This work has been supported in part by grants from the French National Agency for Research called 'Investissements d'Avenir' Labex IRON n°ANR-11-LABX-0018-01 and Equipex ArronaxPlus n°ANR-11-EQPX-0004, and by a grant from the 'DHU Oncogreffe' of the Nantes University Hospital., ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, and 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)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, carcinoembryonic antigen, immuno-PET, colonic cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, liver metastases, 18 FDG-PET
Abstract

International audience; ABSTRACT Purpose: The aim of this study was to compare the performances pretargeted immunoPET 68 Ga-PETimaging (68 Ga-pPET) with anti carcino-embryonic antigen (CEA) and anti-histamine-succinyl-glycine (HSG) recombinant humanized bispecific monoclonal antibody (TF2) and 68 Ga-labeled HSG peptide (IMP288) to conventional 18 FDG-PET in an orthotopic murine model of liver metastases of human colonic cancer. Methods: Hepatic tumor burden following intra-portal injection of luciferase-transfected LS174T cells in nude mice was confirmed using bioluminescence. One group of animals was injected intravenously with TF2 and with 68 Ga-IMP288 24 hours later (n=8). Another group received 18 FDG (n=8), and a third had both imaging modalities (n=7). PET acquisitions started 1 hour after injection of the radioconjugate. Biodistributions in tumors and normal tissues were assessed one hour after imaging. Results: Tumor/organ ratios were significantly higher with 68 Ga-pPET compared to 18 FDG-PET (P

Published
2018
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12. PET Imaging of Multiple Myeloma : Comparison of 89Zr- and 64Cu-labeled anti-CD138 Conjugates to 64CuCl2 and 18F-FDG in a Preclinical Syngeneic Model

Author

Bailly, Clément, Gouard, Sébastien, Chalopin, Benjamin, Carlier, Thomas, Sai-Maurel, Catherine, Remaud-Le Saec, Patricia, Bourgeois, Mickaël, Chouin, Nicolas, Tripier, Raphaël, Haddad, Ferid, Faivre-Chauvet, Alain, Kraeber-Bodéré, Françoise, Caroline, Bodet-Milin, Chérel, Michel, Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), 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), Bernardo, Elizabeth, 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 Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

s of Annual Congress of the European Association of Nuclear Medicine October 13 – 17, 2018 Düsseldorf, Germany; International audience; Purpose: Although recent data from the literature suggest that 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 in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated 2 conjugates of an anti-CD138 murine antibody (9E7.4) and compared them to metabolic tracers (64CuCl2and 18F-FDG) for PET imaging in a MM syngeneic mouse model. Subjects and Methods: 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for copper-64 (64Cu) and zirconium- 89 (89Zr) labeling. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies and 64CuCl2 were evaluated via PET imaging and biodistribution studies in C57BL / KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions. These results were compared to 18F-FDG-PET imaging. Autoradiography and histology of representative tumors were secondly conducted. Results: In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and89Zr-DFO-9E7.4displayed comparable good tumor uptake of subcutaneous tumors. On the opposite, only low-level concentrations of 64CuCl2 were accumulated in MM lesions. PET/CT imaging of the disseminated model with 64Cu TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed high uptake of the probes at the site of intra-medullary lesions, greater than that demonstrated with 18F-FDG-PET and correlating with the bioluminescence imaging of the tumor. Histopathologic analysis of the immuno-PET-positive lesions also confirmed the presence of plasma cell infiltrates within the bone marrow. Comparison of both 9E7.4 conjugates revealed higher non specific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4 (3.1±1.15 vs 1.48±0.29 respectively at 24h PI; p=0.0061; non-parametric test) while the opposite was observed for tumor-to-blood ratio (1.42±0.24 vs 4.08±1.09 respectively at 24h PI; p=0.0391; non-parametric test). Such observations were consistent with the known in vivo gradual transchelation of 89Zr over time which could reduce the efficacy of a 89Zr-labeled immuno-PET probe as an effective tool for bone lesions imaging. Conclusion: 64Cu- and 89Zr-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming 18F-FDG-PET and 64CuCl2 in this preclinical model. 64Cu- anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific and promising new imaging radiopharmaceutical agent in MM.

Published
2018
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13. Sensitivity of pretargeted immunoPET using 68Ga-peptide to detect colonic carcinoma liver metastases in a murine xenograft model: Comparison with 18FDG PET-CT

Author

Foubert, Fanny, primary, Gouard, Sébastien, additional, Saï-Maurel, Catherine, additional, Chérel, Michel, additional, Faivre-Chauvet, Alain, additional, Goldenberg, David M., additional, Barbet, Jacques, additional, Bailly, Clément, additional, Bodet-Milin, Caroline, additional, Carlier, Thomas, additional, Kraeber-Bodéré, Françoise, additional, Touchefeu, Yann, additional, and Frampas, Eric, additional

Published
2018
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14. Cyclam te1pa for 64 Cu PET imaging. Bioconjugation to antibody, radiolabeling and preclinical application in xenografted colorectal cancer

Author

Frindel, Mathieu, Le Saec, Patricia, Beyler, Maryline, Navarro, Anne-Sophie, Sai-Maurel, Catherine, Alliot, Cyrille, Chérel, Michel, Gestin, Jean-François, Faivre-Chauvet, Alain, Tripier, Raphaël, Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), 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), Cyclotron ARRONAX [Saint-Herblain], ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; te1pa is a monopicolinate cyclam previously presented as a better 64 Cu chelator than dota, nota and other chelators with an improved biodistribution and in vivo resistance to transchelation. This study aimed to determine whether te1pa could improve the in vivo stability of 64 Cu chelation concerning radioimmunoconjugates in order to obtain better contrast in PET imaging. te1pa was activated on its remaining acid function to obtain a N-hydroxysulfosuccinimide ester and was then conjugated to the F6 mouse IgG1a (F6 mAb), directed against CEA (carcinoembryonic antigen), leading to the F6-te1pa immunoconjugate. F6-te1pa was compared to F6–C-dota, i.e. F6 mAb conjugated with a C-functionalized dota which is the only chelator used nowadays in preclinical trials for 64 Cu PET imaging. Immunoconjugates were radiolabeled with 64 Cu showing an equivalent conjugation rate of 1 ligand per mAb. The study of the complexation kinetics highlighted a relatively fast process and 64 Cu–F6-te1pa, exhibiting a specific activity of 69.3 AE 28.9 MBq mg À1 , was proved to be inert since only 4.3% of radioactivity was transchelated from the ligand to EDTA (50 000 equiv., overnight) used as a competitor. All these results are comparable with C-functionalized dota. However, in vivo studies carried out in LS174T tumor-bearing nude mice showed a limited transchelation of superoxide dismutase (SOD) into the liver; 1.6% for 64 Cu–F6-te1pa after 24 h post-injection, compared to 4.3% for 64 Cu–F6–C-dota. The uptake of 64 Cu–F6-te1pa in tumors and radioactivity distribution in organs after 24 and 48 h was satisfactory and equivalent to various standards presented in the literature. Finally, PET-phenotypic images obtained with 64 Cu–F6-te1pa at 24 h post-injection showed an excellent contrast between tumors and the healthy tissues around, which agrees well with the results of the biodistribution. The usefulness of te1pa for PET phenotypic imaging using 64 Cu has been validated. The synthesis of a bifunctional derivative of te1pa will be the next step of this work to keep the ligand properties intact.

Published
2017
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15. Production and characterization of monoclonal antibodies specific for canine CD138 (syndecan-1) for nuclear medicine preclinical trials on spontaneous tumours

Author

Diab, Maya, Nguyen, Frédérique, Berthaud, Maxime, Maurel, Catherine, Gaschet, J., Verger, Elise, Ibisch, Catherine, Chérel, Michel, Abadie, Jérôme, Davodeau, François, Rousseau, Caroline, Bernardo, Elizabeth, 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), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
Mammary Neoplasms, Animal, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mice, Dogs, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, hemic and lymphatic diseases, Animals, Humans, Dog Diseases, Mice, Inbred BALB C, Hybridomas, B-cell lymphoma, comparative, Antibodies, Monoclonal, syndecan-1, Radioimmunotherapy, Flow Cytometry, monoclonal antibody, dog, oncology, Female, Lymphoma, Large B-Cell, Diffuse, Epitope Mapping, diffuse large
Abstract

International audience; We isolated 11 antibodies specific for canine CD138 (cCD138) to validate the interest of CD138 antigen targeting in dogs with spontaneous mammary carcinoma. The affinity of the monoclonal antibodies in the nanomolar range is suitable for immunohistochemistry and nuclear medicine applications. Four distinct epitopes were recognized on cCD138 by this panel of antibodies. CD138 expression in canine healthy tissues is comparable to that reported in humans. CD138 is frequently expressed in canine mammary carcinomas corresponding to the human triple negative breast cancer subtype, with cytoplasmic and membranous expression. In canine diffuse large B-cell lymphoma, CD138 expression is associated with the 'non-germinal center' phenotype corresponding to the most aggressive subtype in humans. This homology of CD138 expression between dogs and humans confirms the relevance of tumour-bearing dogs as spontaneous models for nuclear medicine applications, especially for the evaluation of new tumour targeting strategies for diagnosis by phenotypic imaging and radio-immunotherapy.

Published
2016
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16. Cyclam te1pa for64Cu PET imaging. Bioconjugation to antibody, radiolabeling and preclinical application in xenografted colorectal cancer

Author

Frindel, Mathieu, primary, Le Saëc, Patricia, additional, Beyler, Maryline, additional, Navarro, Anne-Sophie, additional, Saï-Maurel, Catherine, additional, Alliot, Cyrille, additional, Chérel, Michel, additional, Gestin, Jean-François, additional, Faivre-Chauvet, Alain, additional, and Tripier, Raphaël, additional

Published
2017
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17. Étude d’un des sarcophages en plomb d’Époque moderne de l’hotel-dieu de Tonnerre (Yonne)

Author

Maurel, Catherine, Garcin, Virginie, Duday, Henri, Kielb, Magalie, and Pernot, Michel

Subjects
inhumation, lead, modern era, burial, Blei, sarcophagus, metallography, Neuzeit, plomb, métallographie, Körpergrab, sarcophage, anthropobiology, Sarkophag, anthropobiologie
Abstract

L’étude a porté sur l’un des sept sarcophages métalliques d’un ensemble, datant des XVIe-XVIIe s., découvert dans l’Hôtel-Dieu de Tonnerre (Yonne, France). Grâce à des études anthropobiologique, archéologique et métallographique, l’individu et son sarcophage ont été caractérisés.L’identification des techniques de fabrication a permis de différencier les deux sarcophages emboités qui enveloppaient le défunt, bien que le matériau de départ ait été le même ou presque.L’analyse anthropobiologique, résultant d’une fouille exhaustive en laboratoire, a permis de caractériser le sexe et l’âge du sujet, un individu jeune adulte, de sexe masculin, dont l’état sanitaire général est bon, bien que des variations anatomiques non métriques et une pathologie d’ordre traumatique aient été observées ; enfin, le traitement post mortem appliqué au défunt, problématique, a fait l’objet d’un examen particulier. The study concerned one of a set of seven metal sarcophaguses found in a burial space, dating from the 16th–17th centuries, discovered in the Hôtel-Dieu in Tonnerre (Yonne, France). Using anthropological, archaeological and metallographic techniques, the individual and his sarcophagus have been analysed.Identification of the manufacturing techniques enabled differentiation of the two sarcophaguses, one contained within the other, which held the body, though the material seems to have been the same or almost the same in both layers.The anthropobiological analysis, resulting from an exhaustive laboratory study, revealed the sex and approximate age of the subject. He was a young adult male in good general health, though non-metric anatomical variations and a traumatic pathology were observed. Lastly, the post-mortem treatment applied to the corpse, which has raised various questions, was the object of particular attention. Die Untersuchung betraf einen von sieben Metallsarkophagen eines im Hôtel-Dieu von Tonnerre (Departement Yonne, Frankreich) entdeckten und in das 16.-17. Jh. datierten Ensembles. Anthropobiologische, archäologische und metallographische Studien ermöglichten die genaue Beschreibung des Individuums und seines Sarkophags.Obwohl das Ausgangsmaterial der beiden Sarkophage identisch oder fast identisch war, konnten die beiden ineinander verschachtelten Sarkophage, in denen der Verstorbene ruhte, dank der Identifizierung der Herstellungstechniken unterschieden werden.Die aus einer erschöpfenden Laborgrabung resultierende anthropobiologische Analyse hat es erlaubt, das Geschlecht und das Alter des Individuums zu bestimmen : es handelte sich um einen jungen Erwachsenen männlichen Geschlechts, dessen allgemeiner Gesundheitszustand trotz nicht metrischer anatomischer Merkmale und einer traumatischen Pathologie gut war. Schließlich wurde die problematische Behandlung, die dem Toten post mortem zuteil geworden war, einer besonderen Untersuchung unterzogen.

Published
2012

18. Long-Term Toxicity of 213Bi-Labelled BSA in Mice

Author

Dorso, Laëtitia, primary, Bigot-Corbel, Edith, additional, Abadie, Jérôme, additional, Diab, Maya, additional, Gouard, Sébastien, additional, Bruchertseifer, Frank, additional, Morgenstern, Alfred, additional, Maurel, Catherine, additional, Chérel, Michel, additional, and Davodeau, François, additional

Published
2016
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21. Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model

Author

Fichou, Nolwenn, primary, Gouard, Sébastien, additional, Maurel, Catherine, additional, Barbet, Jacques, additional, Ferrer, Ludovic, additional, Morgenstern, Alfred, additional, Bruchertseifer, Frank, additional, Faivre-Chauvet, Alain, additional, Bigot-Corbel, Edith, additional, Davodeau, François, additional, Gaschet, Joëlle, additional, and Chérel, Michel, additional

Published
2015
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22. Combining α-Radioimmunotherapy and Adoptive T Cell Therapy to Potentiate Tumor Destruction

Author

Ménager, Jérémie, primary, Gorin, Jean-Baptiste, additional, Maurel, Catherine, additional, Drujont, Lucile, additional, Gouard, Sébastien, additional, Louvet, Cédric, additional, Chérel, Michel, additional, Faivre-Chauvet, Alain, additional, Morgenstern, Alfred, additional, Bruchertseifer, Frank, additional, Davodeau, François, additional, Gaschet, Joëlle, additional, and Guilloux, Yannick, additional

Published
2015
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25. 213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

Author

Chérel, Michel, primary, Gouard, Sébastien, additional, Gaschet, Joëlle, additional, Saï-Maurel, Catherine, additional, Bruchertseifer, Frank, additional, Morgenstern, Alfred, additional, Bourgeois, Mickael, additional, Gestin, Jean-François, additional, Bodéré, Françoise Kraeber, additional, Barbet, Jacques, additional, Moreau, Philippe, additional, and Davodeau, François, additional

Published
2013
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27. Comparative Toxicity and Efficacy of Combined Radioimmunotherapy and Antiangiogenic Therapy in Carcinoembryonic Antigen–Expressing Medullary Thyroid Cancer Xenograft

Author

Kraeber-Bodéré, Françoise, primary, Bodet-Milin, Caroline, additional, Niaudet, Colin, additional, Saï-Maurel, Catherine, additional, Moreau, Anne, additional, Faivre-Chauvet, Alain, additional, Thomare, Patrick, additional, Deleris, Gerard, additional, Estieu-Gionnet, Karine, additional, Bikfalvi, Andréas, additional, Barbet, Jacques, additional, and Paris, François, additional

Published
2010
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30. Long-Term Toxicity of 213Bi-Labelled BSA in Mice.

Author

Dorso, Laëtitia, Bigot-Corbel, Edith, Abadie, Jérôme, Diab, Maya, Gouard, Sébastien, Bruchertseifer, Frank, Morgenstern, Alfred, Maurel, Catherine, Chérel, Michel, and Davodeau, François

Subjects
SERUM albumin, TOXICITY testing, BISMUTH isotopes, RADIOLABELING, LABORATORY mice, RADIOIMMUNOTHERAPY
Abstract

Background: Short-term toxicological evaluations of alpha-radioimmunotherapy have been reported in preclinical assays, particularly using bismuth-213 (213Bi). Toxicity is greatly influenced not only by the pharmacokinetics and binding specificity of the vector but also by non-specific irradiation due to the circulating radiopharmaceutical in the blood. To assess this, an acute and chronic toxicity study was carried out in mice injected with 213Bi-labelled Bovine Serum Albumin (213Bi-BSA) as an example of a long-term circulating vector. Method: Biodistribution of 213Bi-BSA and 125I-BSA were compared in order to evaluate 213Bi uptake by healthy organs. The doses to organs for injected 213Bi-BSA were calculated. Groups of nude mice were injected with 3.7, 7.4 and 11.1 MBq of 213Bi-BSA and monitored for 385 days. Plasma parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine, were measured and blood cell counts (white blood cells, platelets and red blood cells) were performed. Mouse organs were examined histologically at different time points. Results: Haematological toxicity was transient and non-limiting for all evaluated injected activities. At the highest injected activity (11.1 MBq), mice died from liver and kidney failure (median survival of 189 days). This liver toxicity was identified by an increase in both ALT and AST and by histological examination. Mice injected with 7.4 MBq of 213Bi-BSA (median survival of 324 days) had an increase in plasma BUN and creatinine due to impaired kidney function, confirmed by histological examination. Injection of 3.7 MBq of 213Bi-BSA was safe, with no plasma enzyme modifications or histological abnormalities. Conclusion: Haematological toxicity was not limiting in this study. Liver failure was observed at the highest injected activity (11.1 MBq), consistent with liver damage observed in human clinical trials. Intermediate injected activity (7.4 MBq) should be used with caution because of the risk of long-term toxicity to kidneys. [ABSTRACT FROM AUTHOR]

Published
2016
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33. Use of multi‐cell spheroids of ovarian carcinoma as an intraperitoneal radio‐immunotherapy model: Uptake, retention kinetics and dosimetric evaluation

Author

Bardiès, Manuel, primary, Thedrez, Philippe, additional, Gestin, Jean‐Francois, additional, Marcille, Berthe‐Marie, additional, Guerreau, Dominique, additional, Faivre‐Chauvet, Alain, additional, Mahe, Marc, additional, Sai‐Maurel, Catherine, additional, and Chatal, Jean‐François, additional

Published
1992
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39. SPECT-CT Imaging of Dog Spontaneous Diffuse Large B-Cell Lymphoma Targeting CD22 for the Implementation of a Relevant Preclinical Model for Human.

Author

Etienne F, Berthaud M, Nguyen F, Bernardeau K, Maurel C, Bodet-Milin C, Diab M, Abadie J, Gouilleux-Gruart V, Vidal A, Bourgeois M, Chouin N, Ibisch C, and Davodeau F

Abstract

Antibodies directed against CD22 have been used in radioimmunotherapy (RIT) clinical trials to treat patients with diffuse large B-cell lymphoma (DLBCL) with promising results. However, relevant preclinical models are needed to facilitate the evaluation and optimization of new protocols. Spontaneous DLBCL in dogs is a tumor model that may help accelerate the development of new methodologies and therapeutic strategies for RIT targeting CD22. Seven murine monoclonal antibodies specific for canine CD22 were produced by the hybridoma method and characterized. The antibodies' affinity and epitopic maps, their internalization capability and usefulness for diagnosis in immunohistochemistry were determined. Biodistribution and PET imaging on a mouse xenogeneic model of dog DLBCL was used to choose the most promising antibody for our purposes. PET-CT results confirmed biodistribution study observations and allowed tumor localization. The selected antibody, 10C6, was successfully used on a dog with spontaneous DLBCL for SPECT-CT imaging in the context of disease staging, validating its efficacy for diagnosis and the feasibility of future RIT assays. This first attempt at phenotypic imaging on dogs paves the way to implementing quantitative imaging methodologies that would be transposable to humans in a theranostic approach. Taking into account the feedback of existing human radioimmunotherapy clinical trials targeting CD22, animal trials are planned to investigate protocol improvements that are difficult to consider in humans due to ethical concerns., (Copyright © 2020 Etienne, Berthaud, Nguyen, Bernardeau, Maurel, Bodet-Milin, Diab, Abadie, Gouilleux-Gruart, Vidal, Bourgeois, Chouin, Ibisch and Davodeau.)

Published
2020
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40. TE1PA as Innovating Chelator for 64 Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model.

Author

Navarro AS, Le Bihan T, Le Saëc P, Bris NL, Bailly C, Saï-Maurel C, Bourgeois M, Chérel M, Tripier R, and Faivre-Chauvet A

Subjects
Animals, Cell Line, Tumor, Immunoconjugates chemistry, Immunoconjugates pharmacokinetics, Mice, Multiple Myeloma pathology, Tissue Distribution, Antibodies, Monoclonal chemistry, Chelating Agents chemistry, Copper Radioisotopes, Heterocyclic Compounds, 1-Ring chemistry, Multiple Myeloma diagnostic imaging, Positron-Emission Tomography methods
Abstract

Following the successful synthesis of a C -functionalized version of the TE1PA ligand, a monopicolinate cyclam, we looked to demonstrate its in vivo properties versus DOTA and NOTA, after conjugation on the 9E7.4 rat antibody, an IgG 2a against CD138 murine, which has relevant properties for multiple myeloma targeting. For each ligand, different conjugation approaches had been considered to select the most appropriate for the comparative study. The p -SCN-Bn-TE1PA, NHS-DOTA, and p -SCN-Bn-NOTA were finally chosen for conjugation and radiolabeling tests. For in vivo comparison, we used a model of subcutaneous grafted mice with 5T33 tumor cells. In vitro tests and immuno-PET study highlighted 64 Cu-9E7.4- p -SCN-Bn-NOTA as the least attractive. Further competitive biodistribution and hepatic metabolic studies at 2, 24, and 48 h post-injection (100 μg radiolabeled with 10 MBq of 64 Cu) were then performed with the 64 Cu-9E7.4- p -SCN-Bn-TE1PA and 64 Cu-9E7.4-NHS-DOTA. Results show a better in vivo resistance of 64 Cu-9E7.4- p -SCN-Bn-TE1PA to transchelation compared to 64 Cu-9E7.4-NHS-DOTA, especially at later times. This was confirmed with 64 Cu-9E7.4- p -SCN-Bn-NOTA at 48 h PI. 64 Cu-9E7.4- p -SCN-Bn-TE1PA also demonstrated an excellent hepatic clearance. 64 Cu-9E7.4- p -SCN-Bn-TE1PA displayed an overall superiority compared to 64 Cu-9E7.4-NHS-DOTA and 64 Cu-9E7.4- p -SCN-Bn-NOTA in terms of in vivo stability, reinforcing the usefulness of the p- SCN-Bn-TE1PA ligand for 64 Cu immuno-PET imaging.

Published
2019
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41. Sensitivity of pretargeted immunoPET using 68 Ga-peptide to detect colonic carcinoma liver metastases in a murine xenograft model: Comparison with 18 FDG PET-CT.

Author

Foubert F, Gouard S, Saï-Maurel C, Chérel M, Faivre-Chauvet A, Goldenberg DM, Barbet J, Bailly C, Bodet-Milin C, Carlier T, Kraeber-Bodéré F, Touchefeu Y, and Frampas E

Abstract

Purpose: The aim of this study was to compare the performances pretargeted immunoPET 68 Ga-PETimaging ( 68 Ga-pPET) with anti carcino-embryonic antigen (CEA) and anti-histamine-succinyl-glycine (HSG) recombinant humanized bispecific monoclonal antibody (TF2) and 68 Ga-labeled HSG peptide (IMP288) to conventional 18 FDG-PET in an orthotopic murine model of liver metastases of human colonic cancer., Methods: Hepatic tumor burden following intra-portal injection of luciferase-transfected LS174T cells in nude mice was confirmed using bioluminescence. One group of animals was injected intravenously with TF2 and with 68 Ga-IMP288 24 hours later (n=8). Another group received 18 FDG (n=8), and a third had both imaging modalities (n=7). PET acquisitions started 1 hour after injection of the radioconjugate. Biodistributions in tumors and normal tissues were assessed one hour after imaging., Results: Tumor/organ ratios were significantly higher with 68 Ga-pPET compared to 18 FDG-PET ( P <0.05) with both imaging and biodistribution data. 68 Ga-pPET sensitivity for tumor detection was 67% vs. 31% with 18 FDG PET ( P =0.049). For tumors less than 200 mg, the sensitivity was 44% with 68 Ga-pPET vs. 0% for 18 FDG PET ( P =0.031). A strong correlation was demonstrated between tumor uptakes measured on PET images and biodistribution analyses (r 2 =0.85)., Conclusion: 68 Ga-pPET was more sensitive than 18 FDG-PET for the detection of human colonic liver metastases in an orthotopic murine xenograft model. Improved tumor/organ ratios support the use of pretargeting method for imaging and therapy of CEA-expressing tumors., Competing Interests: CONFLICTS OF INTEREST Dr. Goldenberg is an inventor of DNL, and was an officer and employee of Immunomedics, Inc., and of IBC Pharmaceuticals, Inc. He retired from IBC Pharmaceuticals and from Immunomedics after this article was submitted for publications. The other authors have no disclosures to report.

Published
2018
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42. Enhanced antitumor activity of combined pretargeted radioimmunotherapy and paclitaxel in medullary thyroid cancer xenograft.

Author

Kraeber-Bodéré F, Saï-Maurel C, Campion L, Faivre-Chauvet A, Mirallié E, Chérel M, Supiot S, Barbet J, Chatal JF, and Thédrez P

Subjects
Animals, Antibodies, Bispecific, Carcinoembryonic Antigen immunology, Carcinoma, Medullary pathology, Combined Modality Therapy, Doxorubicin therapeutic use, Humans, Immunoglobulin G therapeutic use, Iodine Radioisotopes therapeutic use, Mice, Mice, Nude, Neoplasm Transplantation, Pentetic Acid therapeutic use, Thyroid Neoplasms pathology, Transplantation, Heterologous, Tumor Cells, Cultured, Carcinoma, Medullary therapy, Paclitaxel therapeutic use, Pentetic Acid analogs & derivatives, Radiation-Sensitizing Agents therapeutic use, Radioimmunotherapy, Thyroid Neoplasms therapy
Abstract

A significant antitumor effect associated with moderate toxicity was obtained previously with anticarcinoembryonic antigen x antidiethylene-triaminepentaacetic acid (DTPA)-indium F6-734 bispecific antibody and iodine-131-labeled DTPA-indium bivalent hapten in an animal model of medullary thyroid cancer (MTC). The purpose of this study was to determine whether the cytotoxic agents doxorubicin and paclitaxel, also known as radiosensitizers, improve efficacy of pretargeted radioimmunotherapy (RIT) in experimental MTC. Nude mice bearing TT MTC xenograft were treated with F6-734 and iodine-131-labeled DTPA-indium bivalent hapten injected 48 h apart with or without doxorubicin or paclitaxel. The maximum tolerated dose (MTD) of RIT was 92.5 MBq (as determined previously) and that of doxorubicin and paclitaxel 200 and 1000 micrograms, respectively. A control group received no treatment. Animal weight, hematotoxicity, tumor volume, and serum calcitonin were monitored for 5 months. Tumor growth inhibition induced by drugs alone, RIT alone, or combined therapy was characterized by measuring relative tumor volume 20, 40, and 60 days after treatment to detect additivity or synergism. Mean tumor volume doubling time (MTVDT) was 13 +/- 4 days in the control group, 15 +/- 8 days in the group treated with the MTD of doxorubicin, and 32 +/- 13 days in the group treated with the MTD of paclitaxel. After RIT alone at 92.5 MBq, MTVDT was 86 +/- 22 days. After RIT at 74 MBq (80% of MTD), MTVDT was 56 +/- 10 days. MTVDT was not significantly different from this value after RIT plus doxorubicin, 60 +/- 16 days (65 and 100% of the respective single-agent MTDs). Combination of RIT with paclitaxel (65 and 100% of the respective single-agent MTDs) prolonged the suppression of tumor growth. One complete response was observed, and MTVDT was 114 +/- 44 days. This value was significantly longer than the value obtained with RIT alone at 74 MBq (P < 0.05) or with RIT combined with doxorubicin (P < 0.02). The change in serum calcitonin levels paralleled those in tumor volume. Analysis of dose-response curves at days 20 and 40 showed additivity between RIT and paclitaxel, and analysis at day 60 suggested a synergistic effect. In conclusion, addition of doxorubicin did not improve RIT efficacy, whereas paclitaxel improved RIT efficacy significantly without increasing toxicity.

Published
2002

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