Synthesis and in vivo evaluation of [18F]N-(2-benzofuranylmethyl)-N′-[4-(2-fluoroethoxy)benzyl]piperazine, a novel σ1 receptor PET imaging agent

N-(2-Benzofuranylmethyl)-N′-[4-(2-fluoroethoxy)benzyl]piperazine (6, σ1Ki = 2.6 nM) was radiolabeled with fluorine-18 to provide a potential σ1 receptor radioligand for use in positron emission tomography (PET). Radiofluorination of the appropriate tosylate precursor furnished [18F]6 with a specific activity of 45 GBq/μmol, in an average radiochemical yield of 18% and greater than 98% radiochemical purity. MicroPET imaging in Papio hamadryas baboon brain revealed [18F]6 uptake consistent with σ receptor distribution, and specificity for σ receptors was demonstrated in a haloperidol pre-treated animal. [18F]6 possesses suitable properties for PET imaging of σ1 receptors, and further investigation of this σ1 receptor tracer is warranted.

Graphical abstractN-(2-Benzofuranylmethyl)-N′-[4-(2-fluoroethoxy)benzyl]piperazine (6, σ1Ki = 2.6 nM) was radiolabeled with fluorine-18 to provide a potential σ1 receptor radioligand for use in positron emission tomography (PET). Radiofluorination of the appropriate tosylate precursor furnished [18F]6 with a specific activity of 45 GBq/μmol, in an average radiochemical yield of 18% and greater than 98% radiochemical purity. MicroPET imaging in Papio hamadryas baboon brain revealed [18F]6 uptake consistent with σ receptor distribution, and specificity for σ receptors was demonstrated in a haloperidol pre-treated animal. [18F]6 possesses suitable properties for PET imaging of σ1 receptors, and further investigation of this σ1 receptor tracer is warranted.Figure optionsDownload full-size imageDownload as PowerPoint slide