TY - JOUR T1 - Simple synthesis and use of [<sup>11</sup>C]carbonyl difluoride for the intracyclic labeling<sup> </sup>of heterocycles JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 136 LP - 136 VL - 61 IS - supplement 1 AU - Erik Jakobsson AU - Shuiyu Lu AU - Sanjay Telu AU - Victor Pike Y1 - 2020/05/01 UR - http://jnm.snmjournals.org/content/61/supplement_1/136.abstract N2 - 136Objectives: Methods for the intracyclic labeling of heterocycles with carbon-11 (t1/2 = 20.4 min) have garnered considerable interest, and various methods with differing scope, advantages, and limitations have been developed based on direct use of [11C]carbon dioxide, [11C]carbon monoxide, or [11C]phosgene.[1] Further simplified and efficient methods are desirable. Here we explored the synthesis of a new labeling synthon, [11C]carbonyl difluoride ([11C]COF2), and its utility for the intracyclic labeling of heterocycles. Methods: [11C]CO was synthesised from cyclotron-produced [11C]CO2 as described by Zeisler et al.[2] We passed [11C]CO in a helium stream over AgF2[3] and led the radioactive effluent into 1,2-diaminobenzene (1) solution. [11C]1,3-Dihydro-2H-benzo[d]imidazol-2-one ([11C]2) was produced, implying that [11C]COF2 had been produced. We investigated how much AgF2 was required to achieve optimal yield of [11C]2 and further optimized the reaction to use only 0.25 mg of 1 in acetonitrile. We tested a wide range of other precursors for similar ring-closing reactions with [11C]COF2. We reported radiochemical yields (RCY) from [11C]CO based on recovery of the desired labeled heterocycle from the HPLC purification of a reaction mixture aliquot. Results: [11C]COF2 was obtained in quantitative yield from [11C]CO when using at least 0.4 g of AgF2. Several [carbonyl-11C]heterocycles were labeled rapidly at room temperature in high RCYs and with excellent radiochemical purities. A prominent β-adrenoceptor radioligand, [11C](S)-CGP12177, was produced in 72 ± 15% RCY and with a molar activity of 218 ± 58 GBq/µmol. Conclusion: This study demonstrates the simple synthesis and use of [11C]COF2 for the intracyclic labeling of heterocycles. The high reproducibility and efficiency of [11C]COF2 synthesis and of its incorporation into 11C-carbonyl heterocycles renders it to be a very attractive labeling synthon for implementation in regular radiotracer synthesis. Acknowledgements: This work was supported by the Intramural Research Program of the National Institutes of Health (NIMH; ZIA MH002793). References: [1] S. Lu, F. G. Siméon, S. Telu, L. Cai, V. W. Pike, Adv. Het. Chem. In press. [2] S. K. Zeisler, M. Nader, A. Theobald, F. Oberdorfer, Appl Radiat Isot. 1997, 48, 1091. [3] O. V. Ruff, G. Miltschitzky, Z. Anorg. Allg. Chem. 1934, 221, 154. ER -