Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib

Authors

Lilie L Lin
Franklin Wong
Ruitao Lin
Timothy Yap
Jennifer K Litton

Publication Date

8-1-2024

Journal

JCO Precision Oncology

DOI

10.1200/PO.24.00303

PMID

39208372

PMCID

PMC12158472

PubMedCentral® Posted Date

6-11-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Purpose: We tested the ability of [18F] 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 [18F]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 [18F]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 [18F]FTT can image target engagement by PARPi, but larger studies are needed to determine whether [18F]FTT uptake can predict response to PARPi and whether uptake of [18F]FTT in bone marrow may be an early predictor of hematologic toxicity.

Keywords

Humans, Female, Phthalazines, Breast Neoplasms, Middle Aged, Poly(ADP-ribose) Polymerase Inhibitors, Adult, BRCA2 Protein, Positron-Emission Tomography, Fluorine Radioisotopes, BRCA1 Protein, Aged, Positron Emission Tomography Computed Tomography, Mutation

Comments

Trial registration: ClinicalTrials.gov NCT03604315.

This article has been corrected. See JCO Precis Oncol. 2024 Oct 16;8:e2400676.

Published Open-Access

yes

Recommended Citation

Lin, Lilie L; Wong, Franklin; Lin, Ruitao; et al., "Pharmacodynamic Activity of [18F]-Fluorthanatrace Poly(ADP-ribose) Polymerase Positron Emission Tomography in Patients With BRCA1/2-Mutated Breast Cancer Receiving Talazoparib" (2024). Faculty, Staff and Student Publications. 4751.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4751