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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. Methods: Here, via the copper-mediated 18F-radiofluorination of aryl boronic esters, we accessed, for the first time (to our knowledge), the 18F-radiolabeled isotopolog 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, nonradiolabeled drug. Results: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% 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 18F-olaparib increased by 70% (P = 0.025). Conclusion: Taken together, we show that 18F-olaparib has great potential for noninvasive tumor imaging and monitoring of radiation damage.

Original publication

DOI

10.2967/jnumed.118.213223

Type

Journal article

Journal

J Nucl Med

Publication Date

04/2019

Volume

60

Pages

504 - 510

Keywords

PARP, PET, cancer, molecular imaging, olaparib, Animals, Boronic Acids, Cell Line, Tumor, Cell Transformation, Neoplastic, Copper, Fluorine Radioisotopes, Gene Expression Regulation, Enzymologic, Mice, Mice, Inbred BALB C, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerases, Positron-Emission Tomography, Radiochemistry, Tumor Hypoxia