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 cytotoxicity of [77Br]WC-DZ-Br and 2.) Conduct in vitro assays to determine [77Br]WC-DZ-Br localization and DNA damage and 3.) start maximum tolerated dose (MTD) studies in mice. The major activities conducted in this reporting period were to radiolabel WC-BZ-Br with bromine-77 (77Br) and determine its cytotoxicity in prostate cancer cells and determine its ability to cause DNA damage. The specific objectives were to 1.) create ERG fusion cells, 2.) determine cytotoxicity in these and wild-type cells, and 3.) determine DNA damage after addition of radioactivity. The significant results of this reporting period are that [77Br]WC-DZ-Br was highly cytotoxic in wild-type prostate cancer cells and that significant DNA damage was reported using three different markers. It should be noted that we ran into technical issues trying to create the ERG fusion cells. Thus at this point all of the data presented is in wild-type cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1117692
Entities
People
- Buck Rogers
- Dong Zhou
- Jinbin Xu
Organizations
- Washington University in St. Louis