Preliminary evaluation of a novel 18F-labeled PARP-1 ligand for PET imaging of PARP-1 expression in prostate cancer

Nucl Med Biol. 2018 Nov:66:26-31. doi: 10.1016/j.nucmedbio.2018.08.003. Epub 2018 Aug 24.

Abstract

Introduction: Poly (ADP-ribose) polymerase-1 (PARP-1) plays many roles in prostate cancer (PC), such as mediating DNA damage repair, transcriptional regulation and nuclear hormone receptor signaling. Because of this, PARP-1 has been targeted for therapy in PC, and non-invasive imaging of PARP-1 could help predict which patients are likely to respond to such therapy. Several PARP-1 positron emission tomography (PET) imaging agents have been developed and show promise for imaging PARP-1 expression in breast, brain, and lung cancer in small animals, but not as yet in prostate cancer. [18F]WC-DZ-F is an analogue of [18F]FluorThanatrace (FTT) and [125I]KX1, which are well-established PARP-1 ligands for measuring PARP-1 expression. Herein, we evaluated the potential of [18F]WC-DZ-F for the imaging PARP-1 expression in PC.

Methods: [18F]WC-DZ-F was synthesized by a two-step sequence. [18F]WC-DZ-F was evaluated by in vitro uptake studies in PC-3 cells and by in vivo biodistribution and microPET imaging using PC-3 tumor xenografts. Ex vivo autoradiography of PC-3 tumors after microPET imaging was also performed.

Results: [18F]WC-DZ-F has high, PARP-1-specific uptake in PC-3 cells. In the microPET imaging study, [18F]WC-DZ-F accumulated in PC-3 xenograft tumors over 2 h, and the uptake was significantly reduced by blocking with olaparib. PC-3 tumors were clearly visualized in microPET images, and the imaging results were further confirmed by autoradiography of PC-3 tumors ex vivo. In the biodistribution study [18F]WC-DZ-F washed out quickly from most tissues within 2 h, except for the liver in which the uptake was not blockable by olaparib.

Conclusions: We synthesized a novel PARP-1 radioligand, [18F]WC-DZ-F. The preliminary evaluation of [18F]WC-DZ-F indicates that it is a suitable PET imaging agent for measuring PARP-1 expression in prostate cancer and should be applicable to other types of cancers.

Keywords: Biodistribution; Cell uptake; PARP-1; PET imaging; Prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Cell Line, Tumor
  • Fluorine Radioisotopes*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Isotope Labeling
  • Ligands
  • Male
  • Mice
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Positron-Emission Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Radiochemistry
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / metabolism*
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Fluorine Radioisotopes
  • Ligands
  • Radiopharmaceuticals
  • Poly (ADP-Ribose) Polymerase-1
  • Fluorine-18