Radiolabeled PARP Inhibitors for Imaging and Targeted Radiotherapy of Prostate Cancer

Abstract

The of this grant is to investigate a 77Br-labeled poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor for Auger radiation targeted radiotherapy of mCRPC. PARP-1 is a nuclear enzyme which initiates DNA repair by binding to the sites of single- or double-strand breaks (SSB/DSB). The major goals of this reporting period were to 1.) Determine the biodistribution of [77Br]WC-DZ-Br in PC-3 and IGR-CaP1 subcutaneous models, 2.) conduct single dose therapy studies of [77Br]WC-DZ-Br in a metastatic model, 3.) conduct a multi-dose therapy study of [77Br]WCDZ-Br in a metastatic model. The major activities conducted in this reporting period were to evaluate [77Br]WC-DZBr in vivo to determine its tissue localization and therapeutic efficacy after a single administration. The significant results of this reporting period were that [77Br]WC-DZ-Br had good, specific uptake in PC-3 and IGR-CaP1 tumors at 4 h after injection and this uptake was higher than all other tissues except for the liver. In addition, in the metastatic IGR-CaP1 model, injection of [77Br] WC-DZ-Br showed a trend of increasing survival, but this did not reach significance.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2022
Accession Number
AD1190441

Entities

People

  • Buck Rogers

Organizations

  • Washington University in St. Louis

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  • Prostate
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Fields of Study

  • Medicine

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  • Medical Imaging.
  • Molecular Biology and Genetics
  • Prostate Cancer Biology.

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  • Biotechnology
  • Biotechnology - Cancer Biotech