Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.

Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with subcutaneous renal cell cancer (RCC) tumors.

Methods: The (88/90)Y and (177)Lu labeling procedures of cG250 conjugated with cyclic diethylenetriaminepentaacetic acid anhydride (cDTPA), isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA), or 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) were characterized. Stability of the labeled conjugates in plasma at 37 degrees C was assessed. Biodistribution and therapeutic efficacy of labeled cG250 were compared in nude mice with SK-RC-52 human RCC xenografts.

Results: Both SCN-Bz-DTPA and DOTA were stable in vitro (<5% release of the radiolabel during 14 and 21 d of incubation) and in vivo (uptake in bone

Conclusions: DOTA-conjugated radiolabeled antibodies were the most stable radioimmunoconjugates in vitro and in vivo as manifested by the lowest bone uptake. However, specific activity was higher for SCN-Bz-DTPA. The RIT studies clearly showed that the therapeutic efficacy of mAb cG250 labeled with (177)Lu, (90)Y, or (186)Re was superior to that of (131)I-cG250. The residualizing radionuclides (177)Lu and (90)Y led to higher radiation doses to the tumor and most likely are better candidates than conventionally radiolabeled (131)I for RIT with cG250 in patients with RCC.