In vivo measurement of nicotinic acetylcholine receptors with [ 18 F]norchloro‐fluoro‐homoepibatidine

Functional changes of nicotinic acetylcholine receptors (nAChR) are important during age‐related neuronal degeneration. Recent studies demonstrate the applicability of the nAChR ligand 2‐[ 18 F]F‐A‐85380 for neuroimaging of patients with dementias. However, its binding kinetics demands a 7‐h acquisition time limiting its practicality for clinical PET studies. Thus, the authors developed [ 18 F]norchloro‐fluoro‐homoepibatidine ([ 18 F]NCFHEB) for nAChR imaging. The kinetics of the two enantiomers of [ 18 F]NCFHEB were compared with 2‐[ 18 F]F‐A85380 in porcine brain to evaluate their potential for human neuroimaging. Twenty‐four juvenile female pigs were studied with PET using [ 18 F]NCFHEB. Nine animals received an additional i.v. injection (1 mg/kg) of the nAChR agonist A81418 before radiotracer administration followed by infusion (2 mg/kg/7h) thereafter. Several compartment models were applied for quantification. (−)‐ and (+)‐[ 18 F]NCFHEB showed a twofold to threefold higher brain uptake than 2‐[ 18 F]F‐A‐85380. All three radiotracers displayed spatially hetereogenous binding kinetics in regions with high, moderate, or low specific binding. The equilibrium of specific binding of (−)‐[ 18 F]NCFHEB was reached earlier than that of (+)‐[ 18 F]NCFHEB or 2‐[ 18 F]F‐A85380. Continuous administration of the nAChR agonist A81418 inhibited the specific binding of (−)‐ and (+)‐[ 18 F]NCFHEB but not of 2‐[ 18 F]F‐A85380. The peripheral metabolism of (+)‐[ 18 F]NCFHEB proceeded somewhat slower than that of the other radiotracers. Both enantiomers of [ 18 F]NCFHEB are appropriate radiotracers for neuroimaging of nAChR in pigs. Their binding profile in vivo appears to be more selective than that of 2‐[ 18 F]F‐A85380. (−)‐[ 18 F]NCFHEB offers a faster equilibrium of specific binding than 2‐[ 18 F]F‐A85380. Synapse 62:205–218, 2008. © 2007 Wiley‐Liss, Inc.