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Intraperitoneal indium-111- and yttrium-90-labeled human IgM (AC6C3-2B12) in nude mice bearing peritoneal
S M Quadri1, A B Malik, H B Chu
1Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Unlabelled:
Radiolabeled monoclonal antibodies are utilized increasingly for the diagnosis and treatment of human cancer. Tumor targeting of radiolabeled human monoclonal IgM improves with compartmental administration and might be useful for the diagnosis or treatment of peritoneal carcinomatosis.
Methods:
A human monoclonal antibody IgM lambda (AC6C3-B12) reactive with human adenocarcinomas was conjugated to isothiocyanato-2-benzyl-3-methyl-diethylenetriamine-penta-a cetic acid and labeled with either 111In or 90Y. Nude mice bearing intra-abdominal lumps of a human colorectal carcinoma cell line (SW620) were used as a model for peritoneal carcinomatosis. A human monoclonal antibody IgM lambda (CR4E8) reactive with human squamous-cell carcinoma was used as a control.
Results:
Indium-111-IgM and 90Y-IgM immunoconjugates were compared in nude mice at 2, 24, 72, 120 and 144 hr after intraperitoneal administration. Both showed high specific tumor uptake. The tumor-effective half-lives of the immunoconjugates 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 90Y-IgM than for 111In-IgM. The tumor uptake of specific AC6C3-2B12 was about fourfold higher than the uptake of aspecific CR4E8 at 24 and 120 hr.
Conclusion:
The combination of 111In- and 90Y-labeled AC6C3-2B12 offers a new opportunity to develop safer and more effective methods for diagnosing and treating human patients with peritoneal carcinomatosis.