title: An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP.
abstract: The radioligand 3-(4-(3-[(18)F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5,6-tetrahydropyridine ([(18)F]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 [(18)F]FP-TZTP, automated using a GE TRACERlab FX(FN) 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 [(18)F]fluoride (K[(18)F]/K(222)) in CH(3)CN at 80 degrees C for 5 min, and purified by HPLC. Formulated [(18)F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29+/-4%, with a specific activity of 138+/-41 GBq/micromol (3732+/-1109 mCi/micromol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.
authors.affiliation: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
authors.forename: Erik M
authors.initials: EM
authors.lastname: van Oosten
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Karin A
authors.initials: KA
authors.lastname: Stephenson
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Andrei K
authors.initials: AK
authors.lastname: Yudin
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D043585:Receptor, Muscarinic M2 / Q000187:drug effects*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D011725:Pyridines; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D013844:Thiazoles; C115177:FP-TZTP