An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP.
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.
van Oosten
Erik M
EM
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.
Wilson
Alan A
AA
Stephenson
Karin A
KA
Mamo
David C
DC
Pollock
Bruce G
BG
Mulsant
Benoit H
BH
Yudin
Andrei K
AK
Houle
Sylvain
S
Vasdev
Neil
N
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
D011725:Pyridines; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D013844:Thiazoles; C115177:FP-TZTP