18 F]fluorination and [ 18 F]fluoroethylation reactions for the synthesis of the PDE10A PET radiotracer [ 18 F]MNI-659

摘要

Abstract Introduction 2-(2-(3-(4-(2-[ 18 F]Fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([ 18 F]MNI-659, [ 18 F] 1 ) is a useful PET radiotracer for imaging phosphodiesterase 10A (PDE10A) in human brain. [ 18 F] 1 has been previously prepared by direct [ 18 F]fluorination of a tosylate precursor 2 with [ 18 F]F ? . The aim of this study was to determine the conditions for the [ 18 F]fluorination reaction to obtain [ 18 F] 1 of high quality and with sufficient radioactivity for clinical use in our institute. Moreover, we synthesized [ 18 F] 1 by [ 18 F]fluoroethylation of a phenol precursor 3 with [ 18 F]fluoroethyl bromide ([ 18 F]FEtBr), and the outcomes of [ 18 F]fluorination and [ 18 F]fluoroethylation were compared. Methods We performed the automated synthesis of [ 18 F] 1 by [ 18 F]fluorination and [ 18 F]fluoroethylation using a multi-purpose synthesizer. We determined the amounts of tosylate precursor 2 and potassium carbonate as well as the reaction temperature for direct [ 18 F]fluorination. Results The efficiency of the [ 18 F]fluorination reaction was strongly affected by the amount of 2 and potassium carbonate. Under the determined reaction conditions, [ 18 F] 1 with 0.82±0.2GBq was obtained in 13.6%±3.3% radiochemical yield ( n =8, decay-corrected to EOB and based on [ 18 F]F ? ) at EOS, starting from 11.5±0.4GBq of cyclotron-produced [ 18 F]F ? . On the other hand, the [ 18 F]fluoroethylation of 3 with [ 18 F]FEtBr produced [ 18 F] 1 with 1.0±0.2GBq and in 22.5±2.5 % radiochemical yields ( n =7, decay-corrected to EOB and based on [ 18 F]F ? ) at EOS, starting from 7.4GBq of cyclotron-produced [ 18 F]F ? . Clearly, [ 18 F]fluoroethylation resulted in a higher radiochemical yield of [ 18 F] 1 than [ 18 F]fluorination. Conclusion [ 18 F] 1 of high quality and with sufficient radioactivity was successfully radiosynthesized by two methods. [ 18 F] 1 synthesized by direct [ 18 F]fluorination has been approved and will be provided for clinical use in our institute.