Synthesis and in vitro evaluation of 18 F‐β‐carboline alkaloids as PET ligands

A one‐step 18 F‐labelling strategy was used to prepare four 18 F‐labelled analogues of 7‐methoxy‐1‐methyl‐ 9H ‐β‐carboline (harmine): 7‐(2‐[ 18 F]fluoroethoxy)‐1‐methyl‐9 H ‐β‐carboline (5), 7‐(3‐[ 18 F]fluoro‐propoxy)‐1‐methyl‐9 H ‐β‐carboline (6), 7‐[2‐(2‐[ 18 F]fluoroethoxy)ethoxy]‐1‐methyl‐9 H ‐β‐carboline (7), and 7‐{2‐[2‐(2‐[ 18 F]fluoroethoxy)ethoxy]‐ethoxy}‐1‐methyl‐9 H ‐β‐carboline (8). These were synthesized as potential positron emission tomography ligands for monoamine oxidase A (MAO‐A). A solution of pure labelled compound in buffer was obtained in <70 min from end of radionuclide production, with a decay‐corrected yield of up to 23%. The average specific binding to MAO‐A in rat brain, determined by autoradiography experiments, was highest for compounds 7 and 8 (89±2 and 96±1%, respectively), which was obtained at <1 nM radioligand concentration. Copyright © 2008 John Wiley & Sons, Ltd.