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Hyperpolarized 13C Metabolic Magnetic Resonance Spectroscopy and Imaging
Published on: December 30, 2016
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.
Purpose:
PARP inhibitor (PARPi) therapy is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) genomic aberrations. However, only a fraction of patients with BRCA1/2 mutations respond to PARPi therapy. In this pilot study, we assess PARP-1 expression in prostate cancer patients with and without HRR genomic alternations using a novel PARP-based imaging agent.
Procedures:
Nine advanced prostate cancer patients were studied with PET/CT and [18F]FluorThanatrace (FTT), an analogue of the PARPi rucaparib. Images were analyzed using maximum standardized uptake values (SUVmax). PARP expression was assessed by immunohistochemistry (IHC) when feasible (n = 4).
Results:
We found great variability in FTT uptake (SUVmax range: 2.3-15.4). Patients with HRR mutations had a significantly higher SUVmax (p = 0.0379) than patients with non-HRR mutations although there was an overlap in FTT uptake between groups. Three patients without HRR and one with HRR mutations had similarly high PARP1 IHC expression.
Conclusions:
FTT-PET/CT may serve as an alternate biomarker for PARP1 expression and a potential method for PARPi treatment selection.
Insights
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.
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.

