title: Anti-CD45 pretargeted radioimmunotherapy using bismuth-213: high rates of complete remission and long-term survival in a mouse myeloid leukemia xenograft model.
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.
authors: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. jpagel@fhcrc.org
authors: John M
authors: JM
authors: Pagel
authors: Aimee L
authors: AL
authors: Kenoyer
authors: Tom
authors: T
authors: Bäck
authors: Donald K
authors: DK
authors: Hamlin
authors: D Scott
authors: DS
authors: Wilbur
authors: Darrell R
authors: DR
authors: Fisher
authors: Steven I
authors: SI
authors: Park
authors: Shani
authors: S
authors: Frayo
authors: Amanda
authors: A
authors: Axtman
authors: Nural
authors: N
authors: Orgun
authors: Johnnie
authors: J
authors: Orozco
authors: Jaideep
authors: J
authors: Shenoi
authors: Yukang
authors: Y
authors: Lin
authors: Ajay K
authors: AK
authors: Gopal
authors: Damian J
authors: DJ
authors: Green
authors: Frederick R
authors: FR
authors: Appelbaum
authors: Oliver W
authors: OW
authors: Press
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