F-18 LABELED BENZAMIDES FOR STUDYING THE DOPAMINE-D(2) RECEPTOR WITH POSITRON EMISSION TOMOGRAPHY

Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan- 3beta-yl)benzamides were prepared, and in vitro binding assays were us ed to measure the affinity of these compounds for dopamine D2, dopamin e D3, serotonin 5-HT2, and alpha2-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivit y needed for in vivo studies of the D2 (and possibly D3) receptors. F- 18-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation o f the corresponding desbenzyl precursors with [F-18]-4-fluorobenzyl io dide. Preliminary in vivo studies demonstrated that [F-18]-23 and [F-1 8]-26b are suitable candidates for further evaluation in positron emis sion tomography imaging studies. The slow rate of washout of [F-18]-34 from nondopaminergic regions and its comparatively high lipophilicity indicates that this compound may not be suitable for imaging studies because of a high level of nonspecific binding.