Radioimmunotherapy of A431 Xenografted Mice with Pretargeted B3 Antibody-Streptavidin and 90Y-labeled 1,4,7,10-Tetraazacyclododecane-N,N′,N″,N‴-tetraacetic Acid (DOTA)-Biotin

We investigated the biodistribution of 88 Y/ 111 In-labeled 1,4,7,10-tetraazacyclododecane- N,N′,N″,N‴ -tetraacetic acid (DOTA)-biotin and therapy with 90 Y-labeled DOTA-biotin in tumor-bearing mice after B3-streptavidin antibody conjugate (B3-SA) pretargeting. B3 antibody, recognizing Lewis y antigen, was conjugated to streptavidin (B3-SA). For pretargeting, 400 μg of the B3-SA was injected i.v. into mice bearing A431 tumor xenografts. After tumor localization of B3-SA, 100 μg of synthetic clearing agent was injected i.v. to clear the unbound B3-SA from the circulation. Four h later, 1 μg of radiolabeled DOTA-biotin was injected i.v. Radioimmunotherapy was performed with doses of 9.25 to 37 MBq of 90 Y-labeled DOTA-biotin. As a result, radiolabeled DOTA-biotin cleared rapidly. All of the normal tissues had 163 days in the 37 MBq 90 Y group ( P 90 Y and B3-SA were cured, and remained healthy for >180 days after therapy, compared with control groups, with ≤29.2 days mean survival time ( P