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.

Athymic nude mice bearing i.p. nodules of SKOV3 NMP2, a human ovarian carcinoma cell line, received single (50-400 microCi) or fractionated (150-510 microCi) 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.

Mice that received at least 300 microCi 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 microCi for single (50-300 microCi) and fractionated administrations (150-510 microCi). The highest fractionated activity produced over three logs of tumor cell kill without significant toxicity.

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