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Title: Final Report for research grant entitled "Development of Reagents for Application of At-211 and Bi-213 to Targeted Radiotherapy of Cancer"

This grant was a one-year extension of another grant with the same title (DE-FG03-98ER62572). The objective of the studies was to continue in vivo evaluation of reagents to determine which changes in structure were most favorable for in vivo use. The focus of our studies was development and optimization of reagents for pretargeting alpha-emitting radionuclides At-211 or Bi-213 to cancer cells. Testing of the reagents was conducted in vitro and in animal model systems. During the funding period, all three specific aims set out in the proposed studies were worked on, and some additional studies directed at development of a method for direct labeling of proteins with At-211 were investigated. We evaluated reagents in two different approaches in 'two step' pretargeting protocols. These approaches are: (1) delivery of the radionuclide on recombinant streptavidin to bind with pretargeted biotinylated monoclonal antibody (mAb), and alternatively, (2) delivery of the radionuclide on a biotin derivative to bind with pretargeted antibody-streptavidin conjugates. The two approaches were investigated as it was unclear which will be superior for the short half-lived alpha-emitting radionuclides.
Authors:
Publication Date:
OSTI Identifier:
1032020
Report Number(s):
DOE/ER63789- Final Report
TRN: US1204358
DOE Contract Number:
FG02-04ER63789
Resource Type:
Technical Report
Research Org:
University of Washington
Sponsoring Org:
USDOE Office of Science
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; ANIMALS; BIOTIN; EVALUATION; IN VITRO; IN VIVO; NEOPLASMS; OPTIMIZATION; PROTEINS; RADIOISOTOPES; RADIOTHERAPY; TESTING Targeted Radionuclide Therapy, Astatine-211, Bismuth-213, Radiolabeling, Therapeutic Radiopharmaceuticals