p-[ 18F]fluorobenzyltrozamicol ([ 18F]FBT): Molecular decomposition-reconstitution approach to vesamicol receptor radioligands for positron emission tomography

Current methods of radioligand synthesis for the vesamicol receptor either utilize bioactive unlabeled precursors and/or generate unlabelled bioactive by-products. The presence of these compounds in the radiotracer preparation increases the risk of adverse pharmacological reactions in animals. To eliminate the risk of such reactions, we have synthesized the novel radioligand [ 18F]FBT from two inactive precursors, [ 18F]fluorobenzyl iodide and trozamicol. (+)- and (−)-[ 18F]FBT were synthesized in 57–85% yield, from [ 18F]fluorobenzyl iodide and (+)- and (−)-trozamicol, respectively. In the rat brain, comparable levels of (−)-[ 18F]FBT were found in the striatum, cortex, cerebellum and hippocampus during a 3 h period. In contrast, the striatum:cerebellum, cortex:cerebellum and hippocampus:cerebellum ratios for (+)-[ 18F]FBT increased from unity at 5 min post-injection to 2.8, 1.4 and 1.7, respectively, at 3 h. Therefore, (+)-[ 18F]FBT may be potentially useful for mapping vesamicol receptor density in vivo.