A simple and efficient automated cGMP‐compliant radiosynthesis of [¹¹C]metomidate using solid phase extraction cartridge purification

Abstract

11 C]metomidate ([ 11 C]MTO) is a radiotracer widely used to detect disorders of adrenocortical origin by positron emission tomography (PET) imaging. [ 11 C]MTO PET/computed tomography (PET/CT) is considered a sensitive and specific noninvasive alternative to adrenal vein sampling (AVS) in the management of primary hyperaldosteronism (PHA). Herein, we report a reliable automated procedure for the routine manufacturing of [ 11 C]MTO in current good manufacturing practice (cGMP) conditions on the commercial Synthra MeI Plus Loop Vessel synthesizer. The method is based on a combination of the captivesolvent 11 C-methylation of the carboxylate salt 1b of the MTO precursor 1a followed by solid phase extraction (SPE) cartridge purification methodology, which substitutes HPLC purification of the crude reaction mixture. Starting from 45 GBq [ 11 C]CO 2 at the end of bombardment (EOB), 3 GBq of pure [ 11 C]MTO was produced in 18 minutes with 12% decay corrected radiochemical yield (RCY) at the end of synthesis (EOS) and with the modest molar activity of 13 GBq/μmol at the time of application. Each dose produced met all established quality control (QC) criteria. The method can easily be implemented into other commercial automated radiosynthesizers for manufacturing carbon-11 labeled radiotracers.