Brief Intraperitoneal Radioimmunotherapy of Small Peritoneal Carcinomatosis Using High Activities of Noninternalizing 125I-Labeled Monoclonal Antibodies

Journal of Nuclear Medicine

Pierre-Emmanuel Colombo¹  Stéphanie Ricaud¹  Jean-Pierre Pouget¹  Isabelle Navarro-Teulon¹  Pierre-Olivier Kotzki¹  Véronique Garambois¹  Manuel Bardiès¹  Muriel Busson¹  Samir Boutaleb¹  Vincent Boudousq¹  François Quenet¹  André Pèlegrin¹  Caroline Bascoul-Mollevi¹ 

关键词: radioimmunotherapy;    Auger electrons;    peritoneal carcinomatosis;   

DOI  :  10.2967/jnumed.110.080226

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

We assessed the efficiency and toxicity of brief intraperitoneal radioimmunotherapy using high activities of 125I-labeled monoclonal antibody (mAb) in the treatment of small-volume peritoneal carcinomatosis. Methods: Brief intraperitoneal radioimmunotherapy consisted of a 185-MBq (740 MBq/mg) intraperitoneal injection of 125I-35A7 (an anti–carcinoembryonic antigen mAb) into athymic nude mice 4 d after peritoneal tumor xenografting and, after 1 h, abundant washing of the peritoneal cavity with saline solution to remove unbound radioactivity. Another group of mice received this treatment plus a 37-MBq intravenous injection of 125I-35A7 on day 7 or 11 after grafting. Control groups received a brief treatment followed by an additional intravenous injection on day 7 of either saline solution or irrelevant 125I-PX. Tumor growth was monitored by bioluminescence imaging and SPECT/CT, and hematologic toxicity was evaluated by complete blood counts. Survival time was reported, and the mice were sacrificed when the bioluminescence signal reached 4.5 × 107 photons/s. The biodistribution of 125I-35A7 mAb after intravenous or brief treatment was assessed, and the mean absorbed irradiation dose by organs and tumors was calculated using the MIRD formalism. Results: Mild, transient hematologic toxicity was observed after the brief treatment plus intravenous 125I-mAb, with no weight loss. Median survival increased from 32 d in the control groups, to 46 d in the brief treatment group, to 66 d in the group additionally receiving intravenous treatment on day 11, to 73 d in the group additionally receiving intravenous treatment on day 7. The brief treatment alone resulted in a 3-fold higher tumor-to-blood uptake ratio than did the standard intravenous treatment, and the mean absorbed irradiation doses by tumors were 11.6 Gy for the brief treatment and 16.7 Gy for the additional intravenous treatment. For healthy tissues other than blood, the mean absorbed irradiation dose did not exceed 1 Gy after brief treatment and 4.2 Gy after intravenous treatment. Conclusion: The efficiency, low toxicity, and high tumor–to–healthy tissue uptake ratio associated with brief intraperitoneal 125I-35A7 radioimmunotherapy suggest that this method can be used in combination with radiation-synergistic drugs in the therapy of small-volume peritoneal carcinomatosis after cytoreductive surgery.

【 授权许可】

Unknown