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

Publication Type:

Journal Article

Source:

Blood, Volume 118, Issue 3, p.703-11 (2011)

Keywords:

2011, Animals, Antibodies, Antigens/CD45, Biologics Production Core Facility, Biotin, Bismuth, Cell Line/Tumor, Center-Authored Paper, Clinical Research Division, Disease Models/Animal, Dose-Response Relationship, Female, Humans, Leukemia/Myeloid/ Acute, Leukemia/Myeloid/Acute, MICE, Mice/Inbred BALB C, Organometallic Compounds, Radioimmunotherapy, Radioisotopes, Remission Induction, September 2011, Shared Resources, Streptavidin, Survival Rate, Xenograft Model Antitumor Assays

Abstract:

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