Pilot Study: PARP1 Imaging in Advanced Prostate Cancer

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

doi:10.1007/s11307-022-01746-w

Cited by 5 publications

(6 citation statements)

References 26 publications

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“…Despite an overlap in prostate cancer patients with and without HRR genomic aberrations, median SUVmax was much higher in the former. Importantly, this corroborated with immunohistochemical findings of PARP upregulation, in which patients with high SUVmax values had higher PARP expression on immunohistochemical analysis [ 72 ]. This potentially implies that this group may benefit from PARP inhibitor therapy.…”

Section: [ 18 F]f-radiolabeled Molecular Probes Fo...supporting

confidence: 77%

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[18F]F-Poly(ADP-Ribose) Polymerase Inhibitor Radiotracers for Imaging PARP Expression and Their Potential Clinical Applications in Oncology

Ndlovu,

Lawal,

Mdanda

et al. 2024

JCM

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Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional “PARP enzyme–inhibitor complex” leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis—for instance, BRCA1/2 used in triple-negative breast cancer—should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [18F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

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Section: [ 18 F]f-radiolabeled Molecular Probes Fo...supporting

confidence: 77%

“…[ 18 F]FTT uptake a surrogate predictor of response to PARP inhibitor adjuvant therapy to radiation [70,72]. Higher SUVs in HRR than non-HRR but overlap was noted [72].…”

Section: Rucaparib [ 18 F]ftt P/cmentioning

confidence: 99%

[18F]F-Poly(ADP-Ribose) Polymerase Inhibitor Radiotracers for Imaging PARP Expression and Their Potential Clinical Applications in Oncology

Ndlovu,

Lawal,

Mdanda

et al. 2024

JCM

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“…18 Novel biomarkers may also help determine which patients may benefit, including novel PETbased molecular imaging to determine PARP expression. 19…”

Section: Parp Inhibition In Prostate Cancermentioning

confidence: 99%

Updates in Precision Oncology in Prostate and Urothelial Cancer

Brown

2024

International Journal of Cancer Care and Delivery

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Basic science, translational, and clinical genomic advances in prostate and urothelial cancer have therapeutic implications. Poly(ADP-ribose) polymerase (PARP) inhibitors target cancer cells with homologous recombination repair genomic deficiencies to induce synthetic lethality. PARP inhibitors are approved for BRCA-altered castration resistant prostate cancer treatment either as single agent or in combination with novel hormonal therapies. Another genomic target in prostate cancer is the androgen receptor, especially overcoming resistance via the AR-V7 splice variant and other mechanisms. Strategies for overcoming this resistance, including N-terminal domain inhibitors and PROTAC degraders, are under investigation. Immune checkpoint inhibition is a treatment option for metastatic castrate resistant prostate cancer for patients with mismatch repair deficiency, and neoantigen-based vaccines are under development to harness the immune system to fight prostate cancer. In urothelial cancer, FGFR3 is an important prognostic and predictive marker, often indicative of luminal tumors by gene expression profiling. Erdafitinib targets FGFR alterations and is approved for treatment of refractory metastatic urothelial cancer. Antibody-drug conjugates, including enfortumab vedotin and sacituzumab govitecan, are additional targeted approaches utilized to manage urothelial cancer.

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“…Cette découverte a entraîné le développement des inhibiteurs de l'enzyme poly (ADP-ribose) polymérase (PARPi) comme l'olaparib, remboursé en France pour le traitement des patients mCRPC ayant une mutation (germinale et/ou somatique) de BRCA2 ou BRCA1. Consécutivement, les chercheurs tentent de développer des radiotraceurs capables de visualiser PARP [83,84]. Zhang et al ont montré que la TEP au [ 18 F]PARPZ, radioligand de PARP-1, permettait de quantifier l'effet de [ 225 Ac]Ac-PSMA-617 dans un modèle murin de cancer de prostate [84].…”

Section: Cibler La Réparation De L'adnunclassified

“…Zhang et al ont montré que la TEP au [ 18 F]PARPZ, radioligand de PARP-1, permettait de quantifier l'effet de [ 225 Ac]Ac-PSMA-617 dans un modèle murin de cancer de prostate [84]. Dehdashti et al ont réalisé une TEP/TDM à la [ 18 F] FluorThanatrace chez 9 patients avec un cancer de prostate métastatique dont 5 mCRPC [83]. Les données disponibles dans la littérature sur ces traceurs PARP restent très limitées.…”

Section: Cibler La Réparation De L'adnunclassified