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Title: 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.

Abstract

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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1001119
Report Number(s):
PNNL-SA-72413
Journal ID: ISSN 0006-4971; BLOOAW; 600306000; TRN: US1100272
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Blood, 116(20):4231-4239; Journal Volume: 116; Journal Issue: 20
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

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., and Press, Oliver W. 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.. United States: N. p., 2010. Web. doi:10.1182/blood-2010-05-282327.
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. 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.. United States. doi:10.1182/blood-2010-05-282327.
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., and Press, Oliver W. Thu . "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.". United States. doi:10.1182/blood-2010-05-282327.
@article{osti_1001119,
title = {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.},
author = {Park, Steven I. and Shenoi, Jaideep and Pagel, John M. and Hamlin, Donald K. and Wilbur, D. Scott and Orgun, Nural and Kenoyer, Aimee L. and Frayo, Shani and Axtman, Amanda and Back, Tom and Lin, Yukang and Fisher, Darrell R. and Gopal, Ajay K. and Green, Damian J. and Press, Oliver W.},
abstractNote = {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.},
doi = {10.1182/blood-2010-05-282327},
journal = {Blood, 116(20):4231-4239},
number = 20,
volume = 116,
place = {United States},
year = {Thu Nov 18 00:00:00 EST 2010},
month = {Thu Nov 18 00:00:00 EST 2010}
}