Radiosynthesis and PET evaluation of [F]Fuzuloparib as a PARP-targeted imaging agent in breast cancer.

Poly(ADP-ribose) polymerase (PARP) imaging shows great potential as a valuable tool for tumor detection, therapeutic monitoring, and patient stratification in clinical oncology. Nonetheless, current PARP-targeted radiotracers face limitations, including suboptimal tumor uptake and insufficient retention within tumor tissue. Fuzuloparib, a PARP inhibitor featuring a trifluoromethyl moiety, offers improved metabolic stability, enhanced lipophilicity, and increased binding affinity. In this work, we developed an F-labeled isotopologue of Fuzuloparib, termed [F]Fuzuloparib, and systematically evaluated its biological performance evaluated its biological performance using MDA-MB-453 cells, which exhibit high PARP-1 expression, through a combination of cell-based and animal experiments. [F]Fuzuloparib showed high tumor accumulation (peak 9.06 ± 0.31 %ID/g at 2 h) and sustained intratumoral retention (7.12 ± 0.31 %ID/g at 6 h), underscoring its potential as a promising PET imaging agent. These preclinical findings highlight the potential of [F]Fuzuloparib as a robust non-invasive imaging agent for identifying PARP-overexpressing malignancies, with implications for optimizing PARP inhibitor therapy and forecasting therapeutic response.