Highly efficient synthesis of [11C]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 diphenylhydroxy acetate) is a hydrophilic, non-metabolized and highly specific muscarinic acetylcholinergic antagonist. Using this quaternary ammonium derivative of QNB, labelled with carbon-11, a positron-emitting isotope (half-life : 20.4 minutes), the potential for quantification of myocardial muscarinic receptors in vivo using the high-resolution, sensitive and quantitative imaging technique PET (positron emission tomography) was previously demonstrated in dogs and validated in humans. In this paper, the radiosynthesis of carbon-11-labelled Me-QNB is investigated and oriented towards the preparation of multi milliCuries of radiotracer. Typically, using no-carrier-added [11C]methyl triflate as the alkylating agent and 0.64 mg (1.89 µmol) of QNB as precursor for labelling at 100°C for 1 minute lead to a 48.5% +/−10% (15 runs) decay-corrected radiochemical yield (based on [11C]methyl triflate). 183 mCi (+/−39) of [11C]Me-QNB ([11C]-1) could be synthesized in only 27 to 28 minutes after EOB and occasionally, up to 340 mCi of [11C]Me-QNB ([11C]-1) were obtained, corresponding to a 85% decay-corrected yield. The associated decay-corrected specific radioactivities obtained were 2658 mCi/µmol (+/−971) at EOB. Copyright © 2001 John Wiley & Sons, Ltd.