Highly efficient synthesis of [C-11]Me-QNB, a selective radioligand for the quantification of the cardiac muscarinic receptors using PET

Me-QNB (N-methyl-quinuclidin-3-yl benzilate or N-methyl-quinuclidin-3-yl di phenylhydroxy acetate) is a hydrophilic, non-metabolized and highly specifi c muscarinic acetylcholinergic antagonist. Using this quaternary ammonium d erivative of QNB, labelled with carbon-11, a positron-emitting isotope (hal f-life : 20.4 minutes), the potential for quantification of myocardial musc arinic receptors in vivo using the high-resolution, sensitive and quantitat ive imaging technique PET (positron emission tomography) was previously dem onstrated in dogs and validated in humans. In this paper, the radiosynthesi s of carbon-11-labelled Me-QNB is investigated and oriented towards the pre paration of multi milliCuries of radiotracer. Typically, using no-carrier-a dded [C-11]methyl triflate as the alkylating agent and 0.64 mg (1.89 mu mol ) of QNB as precursor for labelling at 100 degreesC for 1 minute lead to a 48.5% +/- 10% (15 runs) decay-corrected radiochemical yield (based on [C-11 ]methyl triflate). 183 mCi (+/- 39) of [C-11]Me-QNB ([C-11]-1) could be syn thesized in only 27 to 28 minutes after EOB and occasionally, up to 340 mCi of [C-11]Me-QNB ([C-11]-1) were obtained, corresponding to a 85% decay-cor rected yield. The associated decay-corrected specific radioactivities obtai ned were 2658 mCi/mu mol (+/- 971) at EOB.