An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18 F] FP-TZTP

Abstract

The radioligand 3-(4-(3-[18F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyri- dine ([18F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2)

receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [ 18F]FP-TZTP, automated using a GE TRACERlabTM FXFN radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio)propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [18F]fluoride (K[18F]/K222) in CH3CN at 80 1C for 5 min, and purified by HPLC. Formulated [18F]FP-TZTP was prepared in an uncorrected radiochemical yield of 2974%, with a specific activity of 138741 GBq/mmol (373271109 mCi/mmol) at the end of synthesis (35 min; n 1⁄4 3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.