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Pilot Study: PARP1 Imaging in Advanced Prostate Cancer.

Farrokh Dehdashti1, Melissa A Reimers2, Kooresh I Shoghi3

  • 1Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd, St. Louis, MO, 63110, USA. dehdashtif@wustl.edu.

Molecular Imaging and Biology
|June 14, 2022
PubMed
Summary

This pilot study shows that [18F]FluorThanatrace PET/CT imaging can visualize PARP-1 expression in prostate cancer patients. This novel imaging agent may help select patients for PARP inhibitor therapy.

Keywords:
CancerFTTPARPPARP inhibitor (PARPi) therapyPETPositron emission tomography

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Area of Science:

  • Oncology
  • Nuclear Medicine
  • Genitourinary Cancer

Background:

  • PARP inhibitor (PARPi) therapy is approved for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) genomic aberrations.
  • However, patient response to PARPi therapy varies, indicating a need for better predictive biomarkers.

Purpose of the Study:

  • To assess Poly (ADP-ribose) polymerase-1 (PARP-1) expression in prostate cancer patients using a novel imaging agent.
  • To evaluate the utility of [18F]FluorThanatrace (FTT) PET/CT as a biomarker for PARP-1 expression and potential predictor of PARPi treatment response.

Main Methods:

  • Nine advanced prostate cancer patients underwent PET/CT imaging with [18F]FluorThanatrace (FTT), a PARPi analogue.
  • Image analysis included maximum standardized uptake values (SUVmax).
  • PARP expression was further assessed by immunohistochemistry (IHC) in a subset of patients.

Main Results:

  • Significant variability in FTT uptake was observed (SUVmax range: 2.3-15.4).
  • Patients with HRR mutations showed significantly higher FTT uptake (SUVmax) compared to those without HRR mutations (p=0.0379), despite some overlap.
  • PARP1 IHC expression showed high levels in both HRR-mutated and non-mutated patients, suggesting potential discordance between imaging and IHC.

Conclusions:

  • [18F]FluorThanatrace PET/CT imaging demonstrates potential as a non-invasive biomarker for assessing PARP1 expression in prostate cancer.
  • This imaging approach may aid in selecting patients who are most likely to benefit from PARPi therapy.