MYELOID NEOPLASIA Anti-CD45 pretargeted radioimmunotherapy using bismuth-213: high rates of complete remission and long-term survival in a mouse myeloid leukemia xenograft model

Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)–streptavidin (SA) conjugate and DOTA-biotin labeled with -emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. -emitting radionuclides exhibit high cytotoxicity coupled with a short path length, potentially increasing the therapeutic index and making them an attractive alternative to -emitting radionuclides for patients with acute myeloid leukemia. Accordingly, we have used 213Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of 213Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5% 1.1% of the injected dose of 213Bi was delivered per gram of tumor. -imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after 213Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a -emitting radionuclide (90Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of 213BiDOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 Ci of 213Bior 90Y-DOTA-biotin, 80% and 20%, respectively, survived leukemiafree for more than 100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an -emitting radionuclide may be highly effective and minimally toxic for treatment of acute myeloid leukemia. (Blood. 2011;118(3):703-711)