TY - JOUR T1 - PET Imaging of PARP Expression Using <sup>18</sup>F-Olaparib JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 504 LP - 510 DO - 10.2967/jnumed.118.213223 VL - 60 IS - 4 AU - Thomas C. Wilson AU - Mary-Ann Xavier AU - James Knight AU - Stefan Verhoog AU - Julia Baguña Torres AU - Michael Mosley AU - Samantha L. Hopkins AU - Sheena Wallington AU - Phillip D. Allen AU - Veerle Kersemans AU - Rebekka Hueting AU - Sean Smart AU - Véronique Gouverneur AU - Bart Cornelissen Y1 - 2019/04/01 UR - http://jnm.snmjournals.org/content/60/4/504.abstract N2 - 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. ER -