In-Loop 11CCO2-Fixation: Prototype and Proof-of-Concept

摘要

Carbon-11 labelled carbon dioxide is the most common feedstock for the synthesis of positron emission tomography radiotracers, and can be directly used for ¹¹C-carbonylation. Herein, we report the development of an apparatus that takes advantage of “in-loop” technologies to facilitate robust and reproducible syntheses of ¹¹C-carbonyl-based radiotracers by [¹¹C]CO2-fixation. Our “in-loop” [¹¹C]CO2-fixation method is simple, efficient, and proceeds smoothly at ambient pressure and temperature. We selected model ¹¹C-carbonyl labelled 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, [¹¹C]SL25.1188, as well as two 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).