INTRAPERITONEAL INDIUM-111-LABELED AND YTTRIUM-90-LABELED HUMAN-IGM (AC6C3-2B12) IN NUDE-MICE BEARING PERITONEAL CARCINOMATOSIS

Radiolabeled monoclonal antibodies are utilized increasingly for the d iagnosis and treatment of human cancer. Tumor targeting of radiolabele d human monoclonal IgM improves with compartmental administration and might be useful for the diagnosis or treatment of peritoneal carcinoma tosis. Methods: A human monoclonal antibody IgM lambda (AC6C3-B12) rea ctive with human adenocarcinomas was conjugated to -2-benzyl-3-methyl- diethylenetriamine-penta-acetic acid and labeled with either In-111 or Y-90. Nude mice bearing intra-abdominal lumps of a human colorectal c arcinoma cell line (SW620) were used as a model for peritoneal carcino matosis. A human monoclonal antibody IgM lambda (CR4E8) reactive with human squamous-cell carcinoma was used as a control. Results: Indium-1 11-IgM and Y-90-IgM immunoconjugates were compared in nude mice at 2, 24, 72, 120 and 144 hr after intraperitoneal administration. Both show ed high specific tumor uptake. The tumor-effective half-lives of the i mmunoconjugates were 39 hr for indium and 46 hr for yttrium. Tumor-to- normal organ ratios were high and similar for both reagents. Only the femur uptake at later time points was relatively higher for the Y-90-I gM than for In-111-IgM. The tumor uptake of specific AC6C3-2B12 was ab out fourfold higher than the uptake of aspecific CR4E8 at 24 and 120 h r. Conclusion: The combination of In-111- and Y-90-labeled AC6C3-2B12 offers a new opportunity to develop safer and more effective methods f or diagnosing and treating human patients with peritoneal carcinomatos is.