Journal Article
Blood, vol. 116, iss. 20, pp. 4231-4239, 2010
Authors
Steven I. Park, Jaideep Shenoi, John M. Pagel, Don K. Hamlin, D. Scott Wilbur, Nural Orgun, Aimee L. Kenoyer, Shani Frayo, Amanda Axtman, Tom Bäck, Yukang Lin, Darrell R. Fisher, Ajay K. Gopal, Damian J. Green, Oliver W. Press
Abstract
Abstract
Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 minutes, tumor uptake for 1F5(scFv)4SA was 16.5% ± 7.0% injected dose per gram compared with 2.3% ± .9% injected dose per gram for the control FP. Mice treated with anti-CD20 PRIT and 600 μCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared with controls (mean tumor volume .01 ± .02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared with 23 days for the control FP (P < .0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.
