Comparison of N-[C-11]methyl-norchloroepibatidine and N-[C-11]methyl-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane with N-[C-11]methyl-epibatidine in small animal PET studies

Structural variations of the nicotinic acetylcholine receptor radioligand N -[C-11]methylepibatidine were made to form C-11-labeled N-methyl-norchloroe pibatidine (N-methyl-NorchloroEPB) and N-methyl-2-(2-pyridyl)-7-azabicyclo[ 2.2.1]heptane (N-methyl-2PABH). Radiosyntheses were performed by methylatio n with high radiochemical purities (>98%) and with specific activities betw een 140 and 500 GBq/mu mol at the end of synthesis. The radiochemical yield (decay-corrected, related to [C-11]CH3T) was between 5 and 10%. Positively and negatively radiolabeled enantiomers were prepared in high optical puri ty (>98%ee) by labeling of the appropriate optically active substrates, whi ch were obtained via chiral high performance liquid chromatography. For in vivo studies radioligands were administered intravenously in rats. Brain up take curves were acquired and combined with blocking experiments. Brain upt ake of N-[C-11]methyl-NorchloroEPB was similar to that of N-[C-11]methyl-EP B whereas N-[C-11]methyl-2PABH with the modified pyridine ring had a signif icantly lower uptake. NUCL MED BIOL 27;3:239-247, 2000. (C) 2000 Elsevier S cience Inc. All rights reserved.