Pilot Study: PARP1 Imaging in Advanced Prostate Cancer

Farrokh Dehdashti; Melissa A. Reimers; Kooresh I. Shoghi; Delphine L. Chen; Jingqin Luo; Buck Rogers; Russell K. Pachynski; Sreeja Sreekumar; Cody Weimholt; Dong Zhou

doi:10.1007/s11307-022-01746-w

Pilot Study: PARP1 Imaging in Advanced Prostate Cancer

Farrokh Dehdashti, Melissa A. Reimers, Kooresh I. Shoghi, Delphine L. Chen, Jingqin Luo, Buck Rogers, Russell K. Pachynski, Sreeja Sreekumar, Cody Weimholt, Dong Zhou

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3 Scopus citations

Abstract

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 (SUV_max). PARP expression was assessed by immunohistochemistry (IHC) when feasible (n = 4). Results: We found great variability in FTT uptake (SUV_max range: 2.3–15.4). Patients with HRR mutations had a significantly higher SUV_max (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.

Original language	English
Pages (from-to)	853-861
Number of pages	9
Journal	Molecular Imaging and Biology
Volume	24
Issue number	6
DOIs	https://doi.org/10.1007/s11307-022-01746-w
State	Published - Dec 2022

Keywords

Cancer
FTT
PARP
PARP inhibitor (PARPi) therapy
PET
Positron emission tomography

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title = "Pilot Study: PARP1 Imaging in Advanced Prostate Cancer",

abstract = "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.",

keywords = "Cancer, FTT, PARP, PARP inhibitor (PARPi) therapy, PET, Positron emission tomography",

author = "Farrokh Dehdashti and Reimers, {Melissa A.} and Shoghi, {Kooresh I.} and Chen, {Delphine L.} and Jingqin Luo and Buck Rogers and Pachynski, {Russell K.} and Sreeja Sreekumar and Cody Weimholt and Dong Zhou",

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year = "2022",

month = dec,

doi = "10.1007/s11307-022-01746-w",

language = "English",

volume = "24",

pages = "853--861",

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T2 - PARP1 Imaging in Advanced Prostate Cancer

AU - Dehdashti, Farrokh

AU - Reimers, Melissa A.

AU - Shoghi, Kooresh I.

AU - Chen, Delphine L.

AU - Luo, Jingqin

AU - Rogers, Buck

AU - Pachynski, Russell K.

AU - Sreekumar, Sreeja

AU - Weimholt, Cody

AU - Zhou, Dong

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Cancer

KW - FTT

KW - PARP

KW - PARP inhibitor (PARPi) therapy

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JO - Molecular Imaging and Biology

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IS - 6

ER -

Pilot Study: PARP1 Imaging in Advanced Prostate Cancer

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