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Abstract

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[6.4.1.0^4,13]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.

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