[ 1 1 C]S11568 (3-ethyl 5-methyl 2-[2-(2-aminoethoxy)ethoxymethyl]-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydr opyridine-3,5-dicarboxylate) is a powerful ligand for the visualization of the cardiac calcium channel in vivo using PET. The aim of the present study was to synthesize a lipophilic, nonionized derivative of S11568 to facilitate its penetration into the brain. To increase the lipophilicity and to remove simultaneously the ionic nature of our ligand, the N-tert-butoxycarbonyl (N-Boc) derivative of S11568 was synthesized. An IC 5 0 value of 1.7 nM for this derivative confirmed that both the affinity and selectivity for the calcium channel was unaltered by this chemical modification (S11568 with IC 5 0 value of 9.9 nM). The biologically more active enantiomer of S11568, the levogyre isomer S12968, was labelled with 1 1 C using [ 1 1 C]iodomethane. The lipophilicity of the N-Boc derivative was increased by a factor of three to four when compared to the parent compound (as determined by the measurement of the octanol/buffer partition coefficients). In vivo, this derivative slightly crosses the blood-brain barrier, as demonstrated by a 4-fold increase (with respect to the parent compound S12968) of the radioactivity in the brain using the 1 1 C-labelled N-Boc S12968. This uptake remained too low to be suitable for imaging calcium channels.