Pharmacodynamic Activity of [ 18 F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2 -Mutated Breast Cancer Receiving Talazoparib
Year: 2024
Type: article
Abstract: PURPOSE We tested the ability of [ 18 F] fluorthanatrace (FTT), a radiolabeled analog of poly(ADP-ribose) polymerase (PARP)-1 inhibitors, to demonstrate target engagement on positron emission tomography (PET) scans from patients with newly diagnosed primary breast cancer receiving the PARP inhibitor (PARPi) talazoparib. METHODS Seven patients with germline BRCA1/2 pathogenic variants underwent [ 18 F]FTT PET-computed tomography scanning at baseline, and five underwent repeat scanning 14 days after talazoparib initiation. Maximum uptake on PET was quantified in the primary tumor, involved nodes, contralateral pectoralis muscle, and lumbar vertebra body level 3, and compared between the two time points. RESULTS Blocking of [ 18 F]FTT was observed on the second scan. Potentially strong but nonsignificant correlations were found between changes in tumor volume (on ultrasound at 1 month v baseline) and percentage changes in tumor-to-muscle uptake ratio at 14 days from baseline (Spearman rank correlation coefficient r = 1; P = .083); and between the highest-grade hematologic toxicity and baseline bone marrow-to-muscle (B/M) uptake ratio ( r = 0.72; P = .068) and percentage change in B/M ratio at 14 days from baseline ( r = 0.87; P = .058). CONCLUSION We conclude that [ 18 F]FTT can image target engagement by PARPi, but larger studies are needed to determine whether [ 18 F]FTT uptake can predict response to PARPi and whether uptake of [ 18 F]FTT in bone marrow may be an early predictor of hematologic toxicity.
Source: JCO Precision Oncology
DOI: 10.1200/po.24.00303
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4401988246