PET imaging of PARP expression using [18F]olaparib.

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 18F-radiofluorination of aryl boronic esters, we accessed, for the first time, the 18F-radiolabeled isotopologue of the Food and Drug Administration-approved PARP inhibitor olaparib. The use of the 18F-labeled equivalent of olaparib allows direct prediction of the distribution of olaparib, given its exact structural likeness to the native, non-radiolabeled drug. [18F]Olaparib was taken up selectively in vitro in PARP-1-expressing cells. Irradiation increased PARP-1 expression and [18F]olaparib uptake in a radiation-dose-dependent fashion. PET imaging in mice showed specific uptake of [18F]olaparib in tumors expressing PARP-1 (3.2±0.36%ID/g in PSN-1 xenografts), correlating linearly with PARP-1 expression. Two hours after irradiation of the tumor (10 Gy), uptake of [18F]olaparib increased by 70% (P = 0.025). Taken together, we show that [18F]olaparib has great potential for non-invasive tumor imaging and monitoring of radiation damage.