ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 28 citations in OpenAlex.
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- Baseline PARP-1 PET imaging in patients with advanced solid tumors with DNA damage response mutations.European journal of nuclear medicine and molecular imaging · 2026Article
- Emerging Molecular PET Imaging for Cell Death in Neurodegenerative Diseases.Journal of medicinal chemistry · 2025Review
- Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.Current treatment options in oncology · 2025Review
- PARP1-targeted alpha therapy enhances target expression.EJNMMI research · 2025Article
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- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
- CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Real-world data of poly (ADP-ribose) polymerase inhibitor response in Japanese patients with ovarian cancer.Cancer medicine · 2024Article
- [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023Article
- Aging imaging: the future demand of health management.European journal of nuclear medicine and molecular imaging · 2023Article
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Shedding Light on PARP Inhibitor Response through Functional Imaging.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
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21 authors at 4 institutions in 1 country.
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Abstract
purposePARP inhibitors have become the standard-of-care treatment for homologous recombination deficient (HRD) high-grade serous ovarian cancer (HGSOC). However, not all HRD tumors respond to PARPi. Biomarkers to predict response are needed. [18F]FluorThanatrace ([18F]FTT) is a PARPi-analog PET radiotracer that noninvasively measures PARP-1 expression. Herein, we evaluate [18F]FTT as a biomarker to predict response to PARPi in patient-derived xenograft (PDX) models and subjects with HRD HGSOC. EXPERIMENTAL
designIn PDX models, [18F]FTT-PET was performed before and after PARPi (olaparib), ataxia-telangiectasia inhibitor (ATRi), or both (PARPi-ATRi). Changes in [18F]FTT were correlated with tumor volume changes. Subjects were imaged with [18F]FTT-PET at baseline and after ∼1 week of PARPi. Changes in [18F]FTT-PET uptake were compared with changes in tumor size (RECISTv1.1), CA-125, and progression-free survival (PFS).
resultsA decrease in [18F]FTT tumor uptake after PARPi correlated with response to PARPi, or PARPi-ATRi treatment in PARPi-resistant PDX models (r = 0.77-0.81). In subjects (n = 11), percent difference in [18F]FTT-PET after ∼7 days of PARPi compared with baseline correlated with best RECIST response (P = 0.01), best CA-125 response (P = 0.033), and PFS (P = 0.027). All subjects with >50% reduction in [18F]FTT uptake had >6-month PFS and >50% reduction in CA-125. Utilizing only baseline [18F]FTT uptake did not predict such responses.
conclusionsThe decline in [18F]FTT uptake shortly after PARPi initiation provides a measure of drug-target engagement and shows promise as a biomarker to guide PARPi therapies in this pilot study. These results support additional preclinical mechanistic and clinical studies in subjects receiving PARPi ± combination therapy. See related commentary by Liu and Zamarin, p. 1384.
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