@article {Chan1516, author = {Chung Ying Chan and Zijun Chen and Gianluca Destro and Mathew Veal and Doreen Lau and Edward O{\textquoteright}Neill and Gemma Dias and Michael Mosley and Florian Guibbal and Veronique Gouverneur and Bart Cornelissen}, title = {Imaging PARP with 18F-rucaparib}, volume = {62}, number = {supplement 1}, pages = {1516--1516}, year = {2021}, publisher = {Society of Nuclear Medicine}, abstract = {1516Objectives: The clinical use of PARP inhibitors in BRCA-mutant cancers has opened a new direction for the development of radiolabeled PARP inhibitors for identification and validation of predictive biomarkers to predict synthetic lethality. Recent clinical studies showed that rucaparib, as single-agent, provided promising treatment efficacy with an acceptable safety profile in advanced pancreatic cancer patients with BRCA1/2 mutation (1). Here, we report on the development of a 18F-labeled isotopologue of rucaparib, which allows direct measurement of the distribution of non-radiolabeled rucaparib. Here, we report the in vitro and in vivo evaluations of the radiolabeled PARP agent, 18F-rucaparib, in pancreatic tumour models. Methods: 18F-Rucaparib was synthesised via Cu-mediated 18F-fluorodeboronation of a protected boronic pinacol ester synthon precursor. In vitro, cell uptake of 18F-rucaparib was determined in two pancreatic cancer cell lines, PSN1 and AsPC1, with and without pre-treatment of DNA damaging agents. Specificity of cell uptake was evaluated by adding an excess of cold PARP inhibitors. In vivo, PET/CT images were acquired, followed by ex vivo biodistribution studies.Results: In vitro, 18Frucaparib showed higher uptake in PSN1 cells than AsPC1 cells. Increased uptake of 18Frucaparib was observed in both cell lines when treated with DNA damaging agents. Cell uptake of 18F-rucaparib could be blocked significantly by addition of an excess of one of several PARP inhibitors, indicating specific binding. Biodistribution at 1 h post-intravenous injection showed PSN1 tumour xenograft uptake with tumour-to-blood ratio: 1.53.Conclusion: Taken together, we demonstrate the great potential of [18F]rucaparib as a non-invasive tumour imaging agent for pancreatic cancers.Acknowledgment: This work was supported by Pancreatic Cancer U.K. 1. Shroff RT, Hendifar A, McWilliams RR, Geva R, Epelbaum R, Rolfe L, et al. Rucaparib monotherapy in patients with pancreatic cancer and a known deleterious BRCA mutation. JCO precision oncology 2018;2:1-15.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/62/supplement_1/1516}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }