"In-loop" [11 C]CO2 fixation: Prototype and proof of concept

Abstract

Carbon-11-labeled carbon dioxide is the most common feedstock for the synthesis of positron emission tomography radiotracers and can be directly used for ¹¹ C-carbonylation. Herein, we report the development of an apparatus that takes advantage of "in-loop" technologies to facilitate robust and reproducible syntheses of ¹¹ C-carbonyl-based radiotracers by [¹¹ C]CO₂ -fixation. Our "in-loop" [¹¹ C]CO₂ -fixation method is simple, efficient, and proceeds smoothly at ambient pressure and temperature. We selected model ¹¹ C-carbonyl-labeled carbamates as well as symmetrical and unsymmetrical ureas based on their widespread use in radiotracer design and our clinical research interests for proof of concept. Utility of this method is demonstrated by the synthesis of a reversible radiopharmaceutical for monoamine oxidase B, [¹¹ C]SL25.1188, and 2 novel fatty acid amide hydrolase inhibitors. These radiotracers were isolated and formulated (>3.5 GBq; 100 mCi) with radiochemical purities (>99%) and molar radioactivity (≥80 GBq/μmol; ≥2162 mCi/μmol).

Keywords: CO2-fixation; carbon-11; carbonylation; loop.