PET Imaging of PARP Expression Using F-Olaparib.

Poly(ADP-ribose) polymerase (PARP) inhibitors are increasingly being studied as cancer drugs, as single agents, or as a part of combination therapies. Imaging of PARP using a radiolabeled inhibitor has been proposed for patient selection, outcome prediction, dose optimization, genotoxic therapy evaluation, and target engagement imaging of novel PARP-targeting agents. Here, via the copper-mediated F-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the F-radiolabeled isotopolog of the Food and Drug Administration-approved PARP inhibitor olaparib. The use of the F-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, nonradiolabeled drug. F-olaparib was taken up selectively in vitro in PARP-1-expressing cells. Irradiation increased PARP-1 expression and F-olaparib uptake in a radiation-dose-dependent fashion. PET imaging in mice showed specific uptake of F-olaparib in tumors expressing PARP-1 (3.2% ± 0.36% of the injected dose per gram of tissue in PSN-1 xenografts), correlating linearly with PARP-1 expression. Two hours after irradiation of the tumor (10 Gy), uptake of F-olaparib increased by 70% ( = 0.025). Taken together, we show that F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.