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 NK(1) receptor radioligands 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[(11)C]methyl-piperazine ([(11)C]BMP, [(11)C]) and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [(11)C]methyl ester ([(11)C]BME, [(11)C]) were synthesized for evaluation as new potential PET imaging agents for brain NK(1) receptors. The new tracers [(11)C]BMP and [(11)C]BME were prepared by N-[(11)C]methylation and O-[(11)C]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid using [(11)C]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 [(11)C] and [(11)C] in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show the tracer [(11)C]BMP had better uptake in the animal brain than the tracer [(11)C]BME and gave higher quality rat brain images. Blocking studies by intravenous coinjection of hot tracer [(11)C]BMP with cold drug BMP had no effect on [(11)C]BMP-PET rat brain imaging. Likewise, blocking studies by intravenous coinjection of hot tracer [(11)C]BME with cold drug BME also showed no effect on [(11)C]BME-PET rat brain imaging. These results suggest that the localization of [(11)C]BMP and [(11)C]BME in rat brain is mediated by nonspecific processes, and the visualization of [(11)C]BMP-PET and [(11)C]BME-PET on rat brain is related to nonspecific binding.
Department of Radiology, Indiana University School of Medicine, Indianapolis, 46202-2111, USA.
Mingzhang
M
Gao
Bruce H
BH
Mock
Gary D
GD
Hutchins
Qi-Huang
QH
Zheng
D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000032:analysis* / Q000378:metabolism; D012995:Solubility
C505877:(4-(2-(3,5-bis-trifluoromethylbenzyloxy)-1-phenylethyl)piperazine-1-yl)acetic acid methyl ester; C505876:1-(2-(3,5-bis-trifluoromethylbenzyloxy)-1-phenylethyl)-4-methylpiperazine; D002250:Carbon Radioisotopes; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D018040:Receptors, Neurokinin-1