Robert Mach,Wenhua Chu,Dong Zhou,Loren Michel,Delphine Chen
申请号：
US15978374
公开号：
US20180326100A1
申请日:
2018.05.14
申请国别(地区):
US
年份:
2018
代理人:
摘要：
Disclosed are PARP-1 inhibitors, which can be 18F-labeled for use as tracers in positron emission tomographic (PET) imaging. Further disclosed are methods of synthesis. Of the compounds synthesized, 2-[p-(2-Fluoroethoxy)phenyl]-1.3.10-triazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraen-9-one (12) had the highest inhibition potency for PARP-1 (IC50=6.3 nM). Synthesis of [18F]-12 is disclosed under conventional conditions in high specific activity with 40-50% decay-corrected yield. MicroPET imaging using [18F]-12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [18F]-12 in a tumor. Binding can be blocked by olaparib. The compounds have utility for tumor imaging.
