Washington University

Loren Michel

Robert H Mach

Wenhua Chu

Dong Zhou

Delphine Chen

Robert Mach

Disclosed are PARP-1 inhibitors, which can beF-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[6.4.1.0]trideca-2,4(13),5,7-tetraen-9-one (12) had the highest inhibition potency for PARP-1 (IC=6.3 nM). Synthesis of [F]-12 is disclosed under conventional conditions in high specific activity with 40-50% decay-corrected yield. MicroPET imaging using [F]-12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [F]-12 in a tumor. Binding, can be blocked by olaparib. The compounds have utility for tumor imaging.

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Clayton, MO, United States of America

Loren Michel