Radioimmunotherapy of a Human Lung Cancer Xenograft with Monoclonal Antibody RS7: Evaluation of 177Lu and Comparison of Its Efficacy with That of 90Y and Residualizing 131I

Tumor targeting and therapeutic efficacy of 177Lu-labeled mono-clonal antibody (mAb) RS7 (antiepithelial glycoprotein-1) was evaluated in a human nonsmall cell lung carcinoma xenograft model. The potential of 177Lu-labeled RS7 was compared with that of RS7 labeled with 90Y and a residualizing form of 131I. Methods: A 1,4,7,10-tetraazacyclododecane-N,N9,N0,N--tetraacetic acid (DOTA) conjugate of RS7 was used for radiola-beling with 177Lu-acetate or 88/90Y-acetate. Biodistribution and therapy studies were conducted in nude mice with subcutane-ous Calu-3 xenografts. Therapy studies were performed using the maximal tolerated doses (MTDs) of 90Y-DOTA-RS7 (3.9 MBq [105 mCi]) and 177Lu-DOTA-RS7 (10.2 MBq [275 mCi]) and com-pared with the data obtained using the MTD (13.0 MBq [350 mCi]) of a residualizing form of 131I-RS7. Results: Radiolabeling of RS7-DOTA conjugate with 177Lu-acetate was facile. 177Lu