Intralesional radioimmunotherapy with Yttrium-90-labeled human monoclonal IgM in nude mice bearing human tumor xenografts.

Abstract

Biodistribution studies demonstrate that intralesional administration of radiolabeled IgM results in high retention of radioactivity with little normal tissue uptake. This study examines the therapeutic potential of this modality. Nude mice bearing subcutaneous human head and neck squamous cell carcinoma xenografts were treated with single intralesional (IL) injections of tumor-reactive human monoclonal IgM (CR4E8) labeled with 25-394 microCi of yttrium-90 (90Y). Untreated mice, mice treated with IL unlabeled immunoconjugate or IL 90Y-aggregate, 160-400 microCi, served as controls. Mice were monitored for tumor growth and toxicity. Mice received 80 Gy per 100 microCi of 90Y-labeled IgM and 110 Gy per 100 microCi of 90Y-aggregate. All tumors treated with 90Y-labeled IgM responded. In mice that received > or = 100 microCi, tumors macroscopically disappeared within three weeks from treatment with seventy-six percent tumor-free at 216 days. Acute toxicities associated with high activity 90Y-labeled IgM and 90Y-aggregate were moist skin desquamation and reduced blood counts. Late radiation damage to connective tissue was observed in mice treated with > 100 microCi of 90Y-labeled IgM. Intralesional administration of 90Y-labeled IgM can ablate tumors in nude mice with modest acute or late toxicity. Further development of this modality for loco-regional therapy is warranted.