Syntheses of 11C- and 18F-labeled carboxylic esters within a hydrodynamically-driven micro-reactor

Abstract

Carboxylic esters were successfully labeled with one of two short-lived positron-emitters, carbon-11 or fluorine-18, within a hydrodynamically-driven micro-reactor. The non-radioactive methyl ester 4a was obtained at room temperature; its yield increased with higher substrate concentration and with reduced infusion rate. Radioactive methyl ester 4b was obtained from the reaction of 1 (10 mM) with 2b in 56% decay-corrected radiochemical yield (RCY) at an infusion rate of 10 µL min⁻¹, and when the infusion rate was reduced to 1 µL min⁻¹, the RCY increased to 88%. The synthesis of the non-radioactive fluoroethyl ester 5a from 1 and 3a required heating of the micro-reactor on a heating block at 80 °C (14–17% RCY), whilst the corresponding radioactive 5b from 1 and 3b was obtained in 10% RCY. The radioactive ‘peripheral’ benzodiazepine receptor ligand 7b was obtained from the reaction of acid 6 with labeling agent 2b in 45% RCY at an infusion rate of 10 µL min⁻¹. When the infusion rate was reduced to 1 µL min⁻¹, the RCY increased to 65%. The results exemplify a new methodology for producing radiotracers for imaging with positron emission tomography that has many potential advantages, including a requirement for small quantities of substrates, enhanced reaction, rapid reaction optimisation and easy product purification.