An 18F-Labeled Poly(ADP-ribose) Polymerase Positron Emission Tomography Imaging Agent

J Med Chem. 2018 May 10;61(9):4103-4114. doi: 10.1021/acs.jmedchem.8b00138. Epub 2018 Apr 19.

Abstract

Poly(ADP-ribose) polymerase (PARP) is involved in repair of DNA breaks and is over-expressed in a wide variety of tumors, making PARP an attractive biomarker for positron emission tomography (PET) and single photon emission computed tomography imaging. Consequently, over the past decade, there has been a drive to develop nuclear imaging agents targeting PARP. Here, we report the discovery of a PET tracer that is based on the potent PARP inhibitor olaparib (1). Our lead PET tracer candidate, [18F]20, was synthesized and evaluated as a potential PARP PET radiotracer in mice bearing subcutaneous glioblastoma xenografts using ex vivo biodistribution and PET-magnetic resonance imaging techniques. Results showed that [18F]20 could be produced in a good radioactivity yield and exhibited specific PARP binding allowing visualization of tumors over-expressing PARP. [18F]20 is therefore a potential candidate radiotracer for in vivo PARP PET imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic
  • Fluorine Radioisotopes*
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / pathology
  • Humans
  • Isotope Labeling
  • Magnetic Resonance Imaging
  • Mice
  • Phthalazines / chemistry*
  • Phthalazines / pharmacology
  • Piperazines / chemistry*
  • Piperazines / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / chemistry*
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Positron-Emission Tomography / methods*

Substances

  • Fluorine Radioisotopes
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases
  • Fluorine-18
  • olaparib