[ 18 F]FPhEP and [ 18 F]F 2 PhEP, two new epibatidine‐based radioligands: Evaluation for imaging nicotinic acetylcholine receptors in baboon brain

The radioligand 2‐[ 18 F]fluoro‐A‐85380 has been developed for imaging α 4 β 2 nAChRs with PET. However, it has slow kinetics and a large fraction of bound activity is nondisplaceable. In an attempt to address these problems, two epibatidine‐based α 4 β 2 nicotinic antagonists, coded FPhEP and F 2 PhEP, were evaluated in vivo in baboons. They were radiolabeled with fluorine‐18 from the corresponding N ‐Boc‐protected bromo‐derivatives and the no‐carrier‐added K[ 18 F]F‐Kryptofix® 222 complex. Radiochemically pure [ 18 F]FPhEP or [ 18 F]F 2 PhEP was obtained in 80 min in amounts of 1.11–2.22 GBq (111–185 GBq/μmol). After injection of 215 MBq of [ 18 F]FPhEP or [ 18 F]F 2 PhEP, dynamic PET data were acquired. Thalamic radioactivity peaked at 20 min (4.9% ± 0.2% ID/100 mL tissue) for [ 18 F]FPhEP. For [ 18 F]F 2 PhEP, the peak was at 45 min (3.3% ± 0.1% ID/100 mL tissue). Regional distribution of both radiotracers was in accordance with the known distribution of nAChRs. In presaturation experiments, nicotine, cytosine, or FPhEP reduced brain radioactivity of [ 18 F]FPhEP. In a displacement experiment with nicotine only a small amount of [ 18 F]F 2 PhEP was dislodged. In spite of a moderate to high in vitro affinity, both ligands do not fulfill the widely adopted criteria for a PET radioligand. Synapse 61:764–770, 2007. © 2007 Wiley‐Liss, Inc.