PT - JOURNAL ARTICLE AU - Dileep Kumar AU - Ramesh Neelamegam TI - A facile radiosynthesis of <sup>18</sup>F-labeled 2-and 4-fluoro pyrimidines and fused pyrimidines DP - 2021 May 01 TA - Journal of Nuclear Medicine PG - 1449--1449 VI - 62 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/62/supplement_1/1449.short 4100 - http://jnm.snmjournals.org/content/62/supplement_1/1449.full SO - J Nucl Med2021 May 01; 62 AB - 1449Objectives: Pyrimidine and fused pyrimidines continue to attract considerable attention to medicinal chemists due to their wide spectrum of biological activities and therapeutic application. The anticancer properties of pyrimidines are due to the presence of pyrimidine bases in nucleic acids, which form the building blocks of DNA and RNA. We recently reported the radiosynthesis of 2-fluoropyrimine analogue [18F]FMPC for targeting microtubule and 4-fluoropyrimidine analogue [18F]FMPT as COX-2 imaging agent via a chlorine to [18F]fluorine displacement reaction.1,2 Herein, we report the radiosynthesis of a series of 18F-labeled pyrimidines and fused pyrimidines at 2 and 4 positions. Methods: The radiolabeling precursor molecules were commercial or synthesized using reported procedure with minor modifications. The nonradioactive reference standards were synthesized by reacting tetrabutyl ammonium fluoride with corresponding chlorides. Radiosynthesis were performed by reacting chloro-precursor with [18F]KF/K222/K2CO3 or [18F]tetraethylammonium fluoride in acetonitrile or DMSO. All radioproducts were purified via reverse phase semipreparative HPLC. Results: Among the tested ligands, 18F-FMPC exhibited highest radiochemical yield (60+5%, EOS). The radiochemical yield of other compounds varies from 15-50% (EOS). In general, 2-[18F]fluoro position labeling show higher radiochemical yield than the tested 4-[18F]fluoro pyrimidines. The total synthetic time for radioligands were 1h (EOS). All radioligands exhibit &gt;95% chemical and radiochemical purities with molar activities of 2.5+0.5 Ci/micromol (decay corrected to EOS). Conclusions: A general procedure for chlorine to [18F]radiolabeling at 2 and 4 positions of pyrimidines have been developed. Utility of this method was demonstrated in the radiosynthesis of microtubule and cyclooxygenase targeted PET tracers. This method offers the radiosynthesis of a wide variety ligand bearing pyrimidine or fused pyrimidines as potential PET tracers. References 1. Kumar JSD, Mann JJ Radiolabeled microtubule imaging compounds and uses thereof, 2019, WO2019089575. 2. Kumar JSD, Mann JJ, Mintz A. Radiolabeled arylpyrimidines/isoxazoles and uses thereof. 2020, WO 19240.1159.