[F-18] FLUOROALKYL ANALOGS OF THE POTENT 5-HT1A ANTAGONIST WAY-100635- RADIOSYNTHESES AND IN-VIVO EVALUATION

Two analogues of the potent 5-HT1A antagonist WAY 100635 have been syn thesized and radiolabelled with F-18, namely l)-1-peperazinyl]ethyl]-N -(2-pyridinyl)cyclohexane carboxamide ([F-18]FEC) and l)-1-piperazinyl ]ethyl]-N-(2-pyridinyl)cyclohexane carboxamide ([F-18]FPC). Biodistrib ution studies in rats showed selective uptake of both radiotracers in regions known to be rich in 5-HT1A receptors following i.v. injection. The ratio of radioactivity in hippocampus to that in the cerebellum w as 5.5 (for [F-18]FEC) and 7.5 (for [F-18]FPC) at 60 min postinjection . Regional brain heterogeneity of radioactivity could be abolished by pretreatment with WAY 100635 and FPC but was unaffected by pretreatmen t with a variety of drugs including ketanserin, sulpiride, and SCH 233 90. These results are compared vis a vis with those obtained using [C- 11]WAY 100635 to evaluate [F-18]FEC and [F-18]FPC as potential radiotr acers for imaging 5-HT1A receptors by positron emission tomography.