Synthesis and initial PET imaging of new potential NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[11C]methyl-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester

The NK1 receptor radioligands 1-[2-(3,5-bis-trifluorometliyl-beiizyloxy)-1-phenyl-ethyl]-4-[C-11]methyl-piperazine ([C-11]BMP, [C-11]1) and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl-acetic acid [C-11]methyl ester ([C-11]BME, [C-11]2) were synthesized for evaluation as new potential PET imaging agents for brain NK1 receptors. The new tracers [C-11]BMP and [C-11]BME were prepared by N-[C-11]methylation and O-[C-11]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-l-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid using [C-11]methyl triflate and isolated by solid-phase extraction (SPE) purification procedure with 40-55% radiochemical yields, decay corrected to end of bombardment, and a synthesis time of 15-20 min. The initial PET dynamic studies of the tracers [C-11]1 and [C-11]2 in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show the tracer [C-11]BMP had better uptake in the animal brain than the tracer [C-11]BME and gave higher quality rat brain images. Blocking studies by intravenous coinjection of hot tracer [C-11]BMP with cold drug BMP had no effect on [C-11]BMP-PET rat brain imaging. Likewise, blocking studies by intravenous coinjection of hot tracer [C-11]BME with cold drug BME also showed no effect on [C-11]BME-PET rat brain imaging. These results suggest that the localization of [C-11]BMP and [C-11]BME in rat brain is mediated by nonspecific processes, and the visualization of [C-11]BMP-PET and [C-11]BME-PET oil rat brain is related to nonspecific binding. (c) 2005 Elsevier Inc. All rights reserved.