Conventional and Pretargeted Radioimmunotherapy Using Bismuth-213 to Target and Treat Non-Hodgkin Lymphomas Expressing CD20: A Preclinical Model toward Optimal Consolidation Therapy to Eradicate Minimal Residual Disease.

Journal Article · Thu Nov 18 00:00:00 EST 2010 · Blood, 116(20):4231-4239

DOI:https://doi.org/10.1182/blood-2010-05-282327· OSTI ID:1001119

Park, Steven I; Shenoi, Jaideep; Pagel, John M; Hamlin, Donald K; Wilbur, D Scott; Orgun, Nural; Kenoyer, Aimee L; Frayo, Shani; Axtman, Amanda; Back, Tom; Lin, Yukang; Fisher, Darrell R; Gopal, Ajay K; Green, Damian J; Press, Oliver W

Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease (MRD) 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 min, tumor uptake for 1F5(scFv)4SA was 16.5 ± 7.0 % injected dose per gram (ID/g) compared with 2.3 ± 0.9 % ID/g for the control FP. Mice treated with anti-CD20 PRIT and 600 µCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared to controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared to 23 days for the control FP (p<0.0001). 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.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1001119
• Report Number(s): PNNL-SA-72413; BLOOAW; 600306000; TRN: US1100272
• Journal Information: Blood, 116(20):4231-4239, Vol. 116, Issue 20; ISSN 0006-4971
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
BEARINGS
BIOTIN
BISMUTH 213
DISEASES
LYMPHOMAS
MICE
NEOPLASMS
PROTEINS
RADIOACTIVITY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
TARGETS
THERAPY
Radioimmunotherapy
bismuth-213
minimal residual disease
lymphoma