Novel Cyclopentadienyl Tricarbonyl 99mTc Complexes Containing 1-Piperonylpiperazine Moiety: Potential Imaging Probes for Sigma-1 Receptors

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• 作者：Xia Wang ; Dan Li ; Winnie Deuther-Conrad ; Jie Lu ; Ying Xie ; Bing Jia ; Mengchao Cui ; J枚rg Steinbach ; Peter Brust ; Boli Liu ; Hongmei Jia
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：August 28, 2014
• 年：2014
• 卷：57
• 期：16
• 页码：7113-7125
• 全文大小：513K
• ISSN：1520-4804

文摘

We report the design, synthesis, and evaluation of a series of novel cyclopentadienyl tricarbonyl ^99mTc complexes as potent 蟽₁ receptor radioligands. Rhenium compounds 3-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)propylcarbonylcyclopentadienyl tricarbonyl rhenium (10a) and 4-(4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl)butylcarbonylcyclopentadienyl tricarbonyl rhenium (10b) possessed high in vitro affinity for 蟽₁ receptors and moderate to high selectivity for 蟽₂ receptors and the vesicular acetylcholine transporter. Biodistribution studies in mice demonstrated high initial brain uptake for corresponding ^99mTc derivatives [^99mTc]23 and [^99mTc]24 of 2.94 and 2.13% injected dose (ID)/g, respectively, at 2 min postinjection. Pretreatment of haloperidol significantly reduced the radiotracer accumulation of [^99mTc]23 or [^99mTc]24 in the brain. Studies of the cellular uptake of [^99mTc]23 in C6 and DU145 tumor cells demonstrated a reduction of accumulation by incubation with haloperidol, 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (SA4503), or 1,3-di-o-tolyl-guanidine (DTG). Furthermore, blocking studies in C6 glioma-bearing mice confirmed the specific binding of [^99mTc]23 to 蟽₁ receptors in the tumor.