A PET imaging agent for evaluating PARP-1 expression in ovarian cancer

J Clin Invest. 2018 May 1;128(5):2116-2126. doi: 10.1172/JCI97992. Epub 2018 Apr 16.


Background: Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in a broad population of patients with ovarian cancer; however, resistance caused by low enzyme expression of the drug target PARP-1 remains to be clinically evaluated in this context. We hypothesize that PARP-1 expression is variable in ovarian cancer and can be quantified in primary and metastatic disease using a novel PET imaging agent.

Methods: We used a translational approach to describe the significance of PET imaging of PARP-1 in ovarian cancer. First, we produced PARP1-KO ovarian cancer cell lines using CRISPR/Cas9 gene editing to test the loss of PARP-1 as a resistance mechanism to all clinically used PARP inhibitors. Next, we performed preclinical microPET imaging studies using ovarian cancer patient-derived xenografts in mouse models. Finally, in a phase I PET imaging clinical trial we explored PET imaging as a regional marker of PARP-1 expression in primary and metastatic disease through correlative tissue histology.

Results: We found that deletion of PARP1 causes resistance to all PARP inhibitors in vitro, and microPET imaging provides proof of concept as an approach to quantify PARP-1 in vivo. Clinically, we observed a spectrum of standard uptake values (SUVs) ranging from 2-12 for PARP-1 in tumors. In addition, we found a positive correlation between PET SUVs and fluorescent immunohistochemistry for PARP-1 (r2 = 0.60).

Conclusion: This work confirms the translational potential of a PARP-1 PET imaging agent and supports future clinical trials to test PARP-1 expression as a method to stratify patients for PARP inhibitor therapy.

Trial registration: Clinicaltrials.gov NCT02637934.

Funding: Research reported in this publication was supported by the Department of Defense OC160269, a Basser Center team science grant, NIH National Cancer Institute R01CA174904, a Department of Energy training grant DE-SC0012476, Abramson Cancer Center Radiation Oncology pilot grants, the Marsha Rivkin Foundation, Kaleidoscope of Hope Foundation, and Paul Calabresi K12 Career Development Award 5K12CA076931.

Keywords: Diagnostic imaging; Molecular biology; Oncology; Pharmacology; Therapeutics.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Contrast Media / administration & dosage*
  • Drug Resistance, Neoplasm*
  • Female
  • Heterografts
  • Humans
  • Mice
  • Middle Aged
  • Neoplasm Proteins
  • Neoplasm Transplantation
  • Ovarian Neoplasms* / diagnostic imaging
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Poly (ADP-Ribose) Polymerase-1* / antagonists & inhibitors
  • Poly (ADP-Ribose) Polymerase-1* / genetics
  • Poly (ADP-Ribose) Polymerase-1* / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage*
  • Positron Emission Tomography Computed Tomography*


  • Contrast Media
  • Neoplasm Proteins
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1

Associated data

  • ClinicalTrials.gov/NCT02637934