Radioimmunotherapy with 125I-mAbs
| Autor: | André Pèlegrin, Véronique Garambois, Isabelle Navarro-Teulon, Pierre-Olivier Kotzki, Vincent Boudousq, Jean-Pierre Pouget, Caroline Bascoul-Mollevi, Lore Santoro, Samir Boutaleb, Monique Pèlegrin |
|---|---|
| Přispěvatelé: | Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Service de Médecine Nucléaire [Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Electricité de France-Service de Radioprotection., Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Biodistribution
Pathology medicine.medical_specialty medicine.drug_class medicine.medical_treatment health care facilities manpower and services education [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine Monoclonal antibody Article 030218 nuclear medicine & medical imaging Iodine Radioisotopes 03 medical and health sciences Mice 0302 clinical medicine In vivo Cell Line Tumor medicine Bioluminescence imaging Animals Radiology Nuclear Medicine and imaging Tissue Distribution Iodotyrosine Radiometry health care economics and organizations Peritoneal Neoplasms Chemistry Antibodies Monoclonal Biological Transport solid tumors Radioimmunotherapy Molecular biology In vitro Tumor Burden Survival Rate 030220 oncology & carcinogenesis Isotope Labeling Toxicity Female Auger electrons |
| Zdroj: | Journal of Nuclear Medicine Journal of Nuclear Medicine, Society of Nuclear Medicine, 2009, 50 (12), pp.2033-41. ⟨10.2967/jnumed.109.066993⟩ |
| ISSN: | 0161-5505 |
| Popis: | International audience; We have previously shown that, in vitro, monoclonal antibodies (mAbs) labeled with the Auger electron emitter (125)I are more cytotoxic if they remain at the cell surface and do not internalize in the cytoplasm. Here, we assessed the in vivo biologic efficiency of internalizing and noninternalizing (125)I-labeled mAbs for the treatment of small solid tumors. METHODS: Swiss nude mice bearing intraperitoneal tumor cell xenografts were injected with 37 MBq (370 MBq/mg) of internalizing (anti-HER1) (125)I-m225 or noninternalizing (anti-CEA) (125)I-35A7 mAbs at days 4 and 7 after tumor cell grafting. Nonspecific toxicity was assessed using the irrelevant (125)I-PX mAb, and untreated controls were injected with NaCl. Tumor growth was followed by bioluminescence imaging. Mice were sacrificed when the bioluminescence signal reached 4.5 x 10(7) photons/s. Biodistribution analysis was performed to determine the activity contained in healthy organs and tumor nodules, and total cumulative decays were calculated. These values were used to calculate the irradiation dose by the MIRD formalism. RESULTS: Median survival (MS) was 19 d in the NaCl-treated group. Similar values were obtained in mice treated with unlabeled PX (MS, 24 d) and 35A7 (MS, 24 d) or with (125)I-PX mAbs (MS, 17 d). Conversely, mice treated with unlabeled or labeled internalizing m225 mAb (MS, 76 and 77 d, respectively) and mice injected with (125)I-35A7 mAb (MS, 59 d) showed a significant increase in survival. Irradiation doses were comparable in all healthy organs, independently from the mAb used, whereas in tumors the irradiation dose was 7.4-fold higher with (125)I-labeled noninternalizing than with internalizing mAbs. This discrepancy might be due to iodotyrosine moiety release occurring during the catabolism of internalizing mAbs associated with high turnover rate. CONCLUSION: This study indicates that (125)I-labeled noninternalizing mAbs could be suitable for radioimmunotherapy of small solid tumors and that the use of internalizing mAbs should not be considered as a requirement for the success of treatments with (125)I Auger electrons. |
| Databáze: | OpenAIRE |
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