Highly efficient synthesis of [11C]S12968 and [11C]S12967, for the in vivo imaging of the cardiac calcium channels using PET

Abstract

AbstractThe dihydrophyridines S12968 ((−)‐S11568, absolute configuration S) and S12967 ((+)‐S11568, absolute configuration R), 3‐ethyl 5‐methyl (−/+)‐2‐[(2‐(2‐aminoethoxy)ethoxy)methyl]‐4‐(2,3‐dichlorophenyl)‐6‐methyl‐1,4‐dihydropyridine‐3,5‐dicarboxylate, have both an in vitro profile of high potency and of high selectivity for the low‐voltage‐dependent L‐type calcium channel. In this paper, the radiosynthesis of both enantiomers, S12968 and S12967, with carbon‐11, a positron‐emitting isotope (half‐life : 20.4 min) was investigated and oriented towards the preparation of multi milliCuries of radiotracer. Typically, 130–250 mCi (4.81–9.25 GBq) of [11C]S12968 and [11C]S12967 were obtained within 30 min of radiosynthesis (HPLC purification included) with specific radioactivities ranging from 500 to 1000 mCi/μmol (18.5–37.0 GBq/μmol) using no‐carrier‐added [11C]methyl triflate as the alkylating agent and the appropriate, enantiomerically pure carboxylic acid precursor at 100°C for 1 min. Based on preliminary PET experiments, only the levo enantiomer S12968 ((−)‐[11C]‐1) appears to be suitable for myocardial PET imaging as demonstrated in vivo in beagle dogs: with S12968, 85% of the uptake of [11C]S12968 could be inhibited in pretreatment experiments and up to 70% of [11C]S12968 could be displaced. Further investigations are currently underway in order to provide an absolute quantification of ventricular calcium channels with PET. Copyright © 2001 John Wiley & Sons, Ltd.