Synthesis and in Vivo Evaluation of Fluorine-18 and Iodine-123 Labeled 2-Carbo(2-fluoroethoxy)-3-(4'-((Z)-2-iodoethenyl)phenyl)nortropane as a Candidate Serotonin Transporter Imaging Agent

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• 作者：Christophe Plisson ; Jeffrey S. Stehouwer ; Ronald J. Voll ; Leonard Howell ; John R. Votaw ; Michael J. Owens ; Mark M. Goodman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：September 20, 2007
• 年：2007
• 卷：50
• 期：19
• 页码：4553 - 4560
• 全文大小：218K
• 年卷期：v.50,no.19(September 20, 2007)
• ISSN：1520-4804

文摘

2-Carbo(2-fluoroethoxy)-3-(4'-((Z)-2-iodoethenyl)phenyl)nortropane (FEpZIENT, 1) was synthesizedas a serotonin transporter (SERT) imaging agent for both positron emission tomography (PET) and singlephoton emission computerized tomography (SPECT). The binding affinity of 1 to human monoaminetransporters showed a high affinity for the SERT (K_i = 0.08 nM) with respect to the dopamine transporter(DAT) (K_i = 13 nM) and the norepinephrine transporter (NET) (K_i = 28 nM). In vivo biodistribution andblocking studies performed in male rats demonstrated that [¹²³I]1 was selective and specific for SERT. Invivo microPET brain imaging studies in an anesthetized monkey with [¹⁸F]1 showed high uptake in thediencephalon and brainstem with peak uptake achieved at 120 min. A chase study with (R,S)-citalopram·HBr displaced [¹⁸F]1 radioactivity from all SERT-rich brain regions. A chase study with the DAT ligand2-carbophenoxy-3-(4-chlorophenyl)tropane (9, RTI-113) failed to displace [¹⁸F]1, indicating that [¹⁸F]1is specific to the SERT. The in vivo evaluation of [¹⁸F]1 indicates that this radiotracer is a good candidatefor mapping and quantifying CNS SERT.