¹⁸F-Labeled Benzamides for Studying the Dopamine D₂ Receptor with Positron Emission Tomography

Two series of (N-benzylpiperidin-4-yl)- and (9-azabicyclo[3.3.1]nonan-3β-yl)benzamides were prepared, and in vitro binding assays were used to measure the affinity of these compounds for dopamine D₂, dopamine D₃, serotonin 5-HT₂, and (α₂-adrenergic receptors. The results of these studies indicated compounds 23, 26b, and 34 have the selectivity needed for in vivo studies of the D₂ (and possibly D₃) receptors. ¹⁸F-Labeled analogues of 23, 26b and 34 were prepared by N-alkylation of the corresponding desbenzyl precursors with [¹⁸F]-4-fluorobenzyl iodide. Preliminary in vivo studies demonstrated that [¹⁸F]-23 and [¹⁸F]-26b are suitable candidates for further evaluation in positron emission tomography imaging studies. The slow rate of washout of [¹⁸F]-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.