INTRALESIONAL RADIOLABELED HUMAN MONOCLONAL IGM IN HUMAN TUMOR XENOGRAFTS

Background and purpose: Intralesional (i.l.) administration of radiola beled human monoclonal IgM could provide a new method for increasing t he radiation dose delivered to a tumor without exceeding normal tissue tolerance. Materials and methods: Nude mice with subcutaneous human h ead and neck squamous cell carcinoma nodules were injected either intr alesionally or intravenously with a tumor-reactive human monoclonal Ig M (CR4E8) labeled with indium-111 ((111)ln) or yttrium-90 (Y-90). Grou ps of mice were sacrificed at different time points and their tumors a nd major organs were excised and counted for radioactivity. Additional mice that were treated with i.l. Y-90-labeled CR4E8 were sacrificed a t the same time points for tumor autoradiography. Serial whole-body ga mma camera images were obtained from additional mice treated with i.l. In-111-labeled CR4E8. Intralesionally administered In-111-labeled irr elevant IgM (CH-1B9) and Y-90-aggregate served as specificity controls . Results: Intralesional administration of radiolabeled IgM resulted i n prolonged high tumor radioactivity with little normal tissue uptake, with kidney and liver having the highest values. The biodistribution of i.l. CR4E8 was similar whether labeled with In-111 or Y-90. Tumor u ptake of i.l. irrelevant IgM appeared to be lower and tumor retention appeared to be shorter. Intravenous administration of tumor-reactive I gM resulted in very low tumor radioactivity with high liver and modera te spleen uptake. The i.l. administration of Y-90-aggregate produced p rolonged high tumor radioactivity with little normal tissue uptake, wi th bone having the highest value. Tumor autoradiographs demonstrated t hat the radiolabeled IgM diffused through the tumor over time while th e Y-90-aggregate remained localized at the injection site. Gamma camer a scintigraphy corroborated the results of the biodistribution studies . Conclusions: Intralesional but not intravenous administration of In- 111- or Y-90-labeled human IgM results in high tumor radioactivity wit h low normal tissue exposure. Myelotoxicity is not anticipated to be t he dose-limiting normal tissue toxicity of this treatment. Further dev elopment of human IgM for the i.l. treatment of human malignancies app ears to be warranted. (C) 1997 Elsevier Science Ireland Ltd.