Alpha-Particle Immunotherapy for Acute Myeloid Leukemia (AML) with Bismuth-213 (213Bi) and Actinium-225 (225Ac)

Lintuzumab, a humanized anti-CD33 antibody, targets myeloid leukemia cells and has modest activity against AML. To increase the antibody’s potency yet avoid nonspecific cytotoxicity seen with β-emitting isotopes, the α-emitter 213Bi was conjugated to lintuzumab. The safety, feasibility, and antileukemic activity of 213Bi-lintuzumab was demonstrated in a phase I trial (Jurcic, Blood 2002). Furthermore, 213Bi-lintuzumab produced remissions in 24% of AML patients receiving doses ≥ 37 MBq/kg after partial cytoreduction with cytarabine (Rosenblat, Clin Cancer Res 2010). The widespread use of 213Bi, however, is limited by its 46-min half-life. 225Ac (t½=10 d), a radiometal that generates four α-particles, can be conjugated to antibodies using DOTA-SCN. 225Ac-labeled immunoconjugates can kill in vitro at doses at least 1,000 times lower than 213Bi analogs and prolong survival in mouse xenograft models of several cancers (McDevitt, Science 2001). We sought to determine the safety, pharmacology, and biological activity of 225Ac-linutuzumab in patients with AML.

JURCIC J. G.;  ROSENBLAT Todd;  MCDEVITT Michael;  PANDIT-TASKAR N.;  CARRASQUILLO Jorge;  SGOUROS G.;  MORGENSTERN Alfred;  CICIC Dragan;  LARSON S. M.;  SCHEINBERG D. A.; 

2013-06-27

Oak Ridge National Laboratory

JRC82744