Intraperitoneal Radioimmunotherapy with Human Monoclonal IGM in Nude Mice with Peritoneal Carcinomatosis

In an effort to improve loco-regional control of ovarian cancer, intraperitoneal (i.p.) administration of an yttrium-90 (⁹⁰Y) labeled human IgM was studied in a nude mouse model of the disease.

Methods

Athymic nude mice bearing i.p. nodules of SKOV3 NMP2, a human ovarian carcinoma cell line, received single (50-400 μCi) or fractionated (150-510 μCi) administrations of ⁹⁰Y-labeled 2B12. Untreated mice and mice treated with unlabeled immunoconjugate served as controls. Mice were monitored for weight loss, blood counts and survival.

Results

Mice that received at least 300 μCi of ⁹⁰Y-labeled 2B12 in a single administration lost more than 10% of their body weight with some early deaths, both of which were prevented with fractionated administration. Granulocytes and lymphocytes declined with treatment while red blood cell counts were relatively stable. Untreated mice and mice treated with unlabeled immunoconjugate had a median survival time of 20 and 17 days respectively. Treatment with ⁹⁰Y-labeled 2B12 increased median survival by 11-12 days per 100 μCi for single (50-300 μCi) and fractionated administrations (150-510 μCi). The highest fractionated activity produced over three logs of tumor cell kill without significant toxicity.

Conclusion

Intraperitoneal RIT with ⁹⁰Y-labeled 2B12 appears to be an attractive modality to treat peritoneal carcinomatosis and warrants further development.