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

Abstract

AbstractMe‐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.