[11C]Carbon dioxide ([11C]CO2) is a highly attractive building block for radiolabeling as it is produced directly in target. Due to low chemical reactivity and trapping efficiency, the direct incorporation of [11C]CO2 into organic molecules poses a significant challenge. Recently, the direct formation of 11C-labeled carbonyl groups via [11C]CO2-fixation, via organic bases, followed by covalent bond formation, has become established in routine radiopharmaceutical production for preparation of 11C-ureas, carbamates and carboxylic acids. These methods are complementary to the most common radiolabeling strategy using carbon-11, which is heteroatom methylation using [11C]CH3I or [11C]CH3OTf. [11C]CO2-fixation radiochemistry has so far been restricted by semi-manual methods. We herein report the development of a fully-automated [11C]CO2-fixation apparatus that takes advantage of the captive solvent or “in-loop” technologies. The “in-loop” [11C]CO2-fixation apparatus consists of trapping and reacting [11C]CO2 directly in a stainless steel loop, which has been applied in the synthesis of 11C-carbonyl-groups with diverse scaffolds including [11C]carbamates (n=4), [11C]oxazolidinones (n=2), and [11C]ureas (n=7) in good radiochemical yields (RCY) ranging from 10 to 98%. Moreover, this technology can be used to prepare libraries of labeled compounds that can be concurrently used to identify and carry out in vivo evaluation of potent compounds. This presentation will highlight several examples to showcase the substrate scope and diverse radiochemistry that can be achieved using this novel “in-loop” method including the syntheses of two candidate radiotracers for fatty acid amide hydrolase (FAAH). Both FAAH radiotracers were produced in good isolated RCYs (18% and 54%; decay-corrected relative [11C]CO2). The radiochemical purity was &gt;99% and the molar radioactivity was &gt;50 GBq/µmol (1250 Ci/mmol) at the end-of-synthesis. PET imaging in rodents showed good whole brain penetration (2.7 SUVmax) and regional uptake was consistent with FAAH distribution. Overall, this “in-loop” [11C]CO2-fixation method is simple and efficient that allows reliable production of [11C]CO2-fixation products.

11C-Carbonylation via “in-loop” 11CO2-fixation

255th National Meeting (2018)

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