PT - JOURNAL ARTICLE AU - Jimmy Jakobsson AU - SANJAY TELU AU - Shuiyu Lu AU - Susovan Jana AU - Victor Pike TI - Rapid and mild synthesis of unsymmetrical [<sup>11</sup>C]ureas from [<sup>11</sup>C]carbonyl difluoride and amines DP - 2021 May 01 TA - Journal of Nuclear Medicine PG - 149--149 VI - 62 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/62/supplement_1/149.short 4100 - http://jnm.snmjournals.org/content/62/supplement_1/149.full SO - J Nucl Med2021 May 01; 62 AB - 149Objectives: Ureas are prevalent biologically active compounds. Many ureas labeled with carbon-11 (t1/2 = 20.4 min) are therefore potentially useful for PET imaging. However, there is currently no versatile and reliable route for accessing a broad range of [carbonyl-11C]ureas. Our aim was to investigate whether the novel building block [11C]carbonyl difluoride ([11C]COF2) [1, 2] can be used for synthesizing acyclic unsymmetrical [11C]ureas. Methods: [11C]CO was synthesized in 11‒12 min in 71 ± 2% (n = 37) yield by passing cyclotron-produced [11C]CO2 over molybdenum at 875 °C. [11C]CO was then quantitatively converted into [11C]COF2 by passage over AgF2 [1,2] and bubbled into a reaction vial holding an aniline (5-10 µmol) or ammonium tosylate (1-3 µmol) in acetonitrile with or without added pyridine. After introduction of all [11C]COF2 into the reaction vial (5.5 min from release of [11C]CO), a second amine was added (1-10 µmol) and left for 1 min. The reaction mixture was analyzed with HPLC. The time from radionuclide production to HPLC injection was 18-20 min. Radiochemical yields of purified labeled products from starting [11C]CO were calculated. Results: Unsymmetrical [11C]ureas from one aniline and one aliphatic amine or from two different aliphatic amines were all produced in excellent selectivity (&gt;90%) over symmetrical [11C]ureas, and in high radiochemical yields (typically 50-90%) via sequential amine addition. Use of a single aliphatic amine as precursor gave the symmetrical [11C]urea. The reaction between [11C]COF2 and ammonium tosylates, as with anilines, stopped at the intermediate [11C]isocyanate to which addition of a second amine yielded the unsymmetrical [11C]urea. The methods proved compatible with a range of functional groups (e.g., hydroxyl, amide, amine, and carboxyl). Added pyridine was found to generally increase the yield of intermediate [11C]isocyanates by improving the trapping efficiency of [11C]COF2. A structurally complex soluble epoxide hydrolase inhibitor AR-9281 was labeled in 80 ± 2% yield. Conclusion: This study demonstrates that [11C]COF2 can be used to efficiently and quickly synthesize acyclic unsymmetrical [11C]ureas from a broad range of amines via intermediate [11C]isocyanates. The room temperature reaction tolerates water well, is mild, and therefore compatible with a range of functional groups. The reaction provides excellent selectivity over symmetrical byproducts. Acknowledgements: This work was supported by the Intramural Research Program of the National Institutes of Health (NIMH; ZIA MH002793). References: [1] J. E. Jakobsson, S. Lu, S. Telu, V. W. Pike, Angew. Chem. Int. Ed. 2020. 59, 7256-7260. [2] J. E. Jakobsson, S. Lu, S. Telu, V. W. Pike, J. Nucl. Med. 2020, 61 (Suppl. 1), 136