Imaging Pharmacodynamics of a PARP Inhibitor.

Abstract

HomeRadiology: Imaging CancerVol. 3, No. 3 PreviousNext Research HighlightsFree AccessImaging Pharmacodynamics of a PARP InhibitorGary D. LukerGary D. LukerGary D. LukerPublished Online:May 28 2021https://doi.org/10.1148/rycan.2021219010MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Take-Away Points■ Major Focus: To establish the feasibility of PET imaging with fluorine 18 (18F)–FluorThanatrace (FTT) to detect binding of an inhibitor of a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, olaparib, in patients with breast cancer.■ Key Result: Treatment with a PARP inhibitor in patients with metastatic breast cancer blocked binding of 18F-FTT to the PARP enzyme.■ Impact: 18F-FTT may be used to noninvasively image pharmacodynamics of therapy with PARP inhibitors in vivo.PARPs are a family of enzymes involved in structure and repair of DNA. Inhibitors of PARP enzymes are used clinically in patients with breast cancer who have mutations in the breast cancer susceptibility genes BRCA1/2. However, BRCA1/2 mutations do not fully predict response to PARP inhibitors. Some patients with mutations fail to benefit from treatment, while treatment may be effective even without mutations in BRCA1/2. Variability in response highlights the need for a biomarker to predict response to treatment with a PARP inhibitor.In a small prospective clinical study, McDonald et al used 18F-FTT, a PET radiotracer that binds to PARP enzymes, to monitor response to therapy with a PARP inhibitor administered to patients with metastatic breast cancer. Pretreatment images showed heterogeneous uptake of 18F-FTT in metastases, showing that amounts of PARP differ notably in different lesions within in a patient. Follow-up imaging after therapy with a PARP inhibitor reduced uptake of 18F-FTT to background levels. Laboratory studies on tumor tissue from several patients verified that a clinical PARP inhibitor blocked binding of the radiotracer to PARP.The current study analyzed data qualitatively rather than quantitatively, and future studies will need to correlate imaging with patient outcomes or other metrics of response. Despite these limitations, the study establishes an imaging approach to monitor pharmacodynamics of a molecularly targeted therapy in patients with cancer.Highlighted ArticleMcDonald ES, Pantel AR, Shah PD, et al. In vivo visualization of PARP inhibitor pharmacodynamics. JCI Insight 2021;6(8):e146592. doi: https://doi.org/10.1172/jci.insight.146592.Highlighted ArticleMcDonald ES, Pantel AR, Shah PD, et al. In vivo visualization of PARP inhibitor pharmacodynamics. JCI Insight 2021;6(8):e146592.doi: https://doi.org/10.1172/jci.insight.146592. Crossref, Medline, Google ScholarArticle HistoryPublished online: May 28 2021 FiguresReferencesRelatedDetailsRecommended Articles PET Molecular Imaging as a Tool for Precision OncologyRadiology2020Volume: 296Issue: 2pp. 379-380Cancer Genomics and Important Oncologic Mutations: A Contemporary Guide for Body ImagersRadiology2017Volume: 283Issue: 2pp. 314-340PET of Fibroblast-Activation Protein for Breast Cancer Diagnosis and StagingRadiology2021Volume: 302Issue: 1pp. 48-49Imaging Neoadjuvant Therapy Response in Breast CancerRadiology2017Volume: 285Issue: 2pp. 358-375Evaluation of LIBRA Software for Fully Automated Mammographic Density Assessment in Breast Cancer Risk PredictionRadiology2020Volume: 296Issue: 1pp. 24-31See More RSNA Education Exhibits Advanced Prostate Cancer: Update on Evolving Concepts, Rationale, and Challenges of Imaging and Novel Therapeutic StrategiesDigital Posters2018Let’s Talk about Next-Generation Breast Cancer Screening Programs: How Should We Do? What Should We Use?Digital Posters2020Beware the Axillae: Presentations of Breast Cancer Recurrence in the Axilla  Digital Posters2019 RSNA Case Collection Inflammatory breast cancerRSNA Case Collection2020Metformin related FDG avidity in the bowelRSNA Case Collection2021Occult Breast CancerRSNA Case Collection2022 Vol. 3, No. 3 Metrics Altmetric Score PDF download