Preclinical Evaluation of a Targeted Alpha-Emitting Radionuclide in Radiotherapy of Breast Cancer
Final rept. 15 Aug 1998-14 Aug 2000
WASHINGTON UNIV SEATTLE
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The research effort was directed at evaluating reagents and conditions for targeting the alpha-emitting radionuclide Bi-213 to breast cancer. Initial studies used human tumor xenografts MCF-7 in athymic mice to demonstrate tumor targeting and bloodtissue clearance. Other studies evaluated placing MCF-7 cells in a renal capsule to mimic a metastatic site. Seven biotin derivatives designed to carry Bi-213 were synthesized. Four of the derivatives were radiolabeled with In-111, Y-90, and Bi-213. The In-111 labeled derivatives were tested in vivo athymic mice to evaluate biodistribution and to demonstrate stability of radiolabel. One of the biotin derivatives, biotin-lysine-benzyl-CHX-A DTPA appears to have properties that will allow its use in vivo. Another reagent, Bi-2l3 labeled succinylated streptavidin appears to be stable to in vivo demetallation, but does not appear to have a distribution that favors use in vivo. The antibody to be used in the studies, BrE3, was not provided as promised, but two other antibodies, L6 Seattle Genetics and NR-LU-10 NeoRx Corp., were kindly provided for study. Other studies included evaluation of tumor targeting with NR-LU-10-SAv conjugate or biotinylated NR-LU-10, and blood clearance with biotinylatedglycosylated BSA or Starburst Trademark Dendrimer. Additional studies are required to optimize the conditions for use of the new reagents.
- Anatomy and Physiology
- Medicine and Medical Research