Noninternalizing Monoclonal Antibodies Are Suitable Candidates for 125I Radioimmunotherapy of Small-Volume Peritoneal Carcinomatosis

Journal of Nuclear Medicine

Samir Boutaleb¹  Jean-Pierre Pouget¹  Isabelle Navarro-Teulon¹  Vincent Boudousq¹  Pierre-Olivier Kotzki¹  Véronique Garambois¹  André Pèlegrin¹  Lore Santoro¹  Monique Pèlegrin¹  Caroline Bascoul-Mollevi¹ 

关键词: radioimmunotherapy;    Auger electrons;    solid tumors;   

DOI  :  10.2967/jnumed.109.066993

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

We have previously shown that, in vitro, monoclonal antibodies (mAbs) labeled with the Auger electron emitter 125I 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 125I-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) 125I-m225 or noninternalizing (anti-CEA) 125I-35A7 mAbs at days 4 and 7 after tumor cell grafting. Nonspecific toxicity was assessed using the irrelevant 125I-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 × 107 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 125I-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 125I-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 125I-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 125I-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 125I Auger electrons.

【 授权许可】

Unknown