Monoclonal antibody-targeted radiotherapy of renal cell carcinoma using a nude mouse model

Radiation dosimetry and monoclonal antibody (MAB)-targeted radiotherapy studies were performed to evaluate the feasibility of using tumor-preferential MAB as targeting agents for internal radiotherapy of renal cell carcinoma (RCC). Two human RCC xenograft lines, TK-177G and TK-82, were established in nude mice and studied using MAB A6H as a targeting agent. This MAB has previously demonstrated excellent in vivo localization to RCC xenografts. Two doses of A6H (13 to 19 micrograms) labeled with iodine 131 (110 to 130 microCi) caused the tumor to regress or arrested the tumor growth in both xenografts. Similar doses (18 to 43 micrograms; 120 microCi) of 131I-labeled control MAB AFP-22 or of unlabeled A6H did not inhibit tumor growth. While most mice in the control groups had tumors greater than 250 mg in weight by day 43, none of the tumors in mice treated with 131I-labeled A6H grew to that size during the 3-month observation period. Sequential computerized scintigraphy was used to calculate the amount of radioisotope localized in tumor versus normal mouse tissue. Therapeutic doses of 131I-labeled A6H delivered a median calculated radiation dose of 38 cGy/microCi (range, 28 to 57) injected dose to RCC xenografts, and a median of 0.9 cGy/microCi to normal mouse tissues. These findings suggest that A6H is able to target radioisotopes highly specifically to RCC and achieve a therapeutic effect in the experimental setting.