Re/99Tcm(CO)3+黄酮复合物的合成及其与Aβ斑块的结合特性

Preparation of Re/99Tcm(CO)3+ Complexed Flavone and Its Characteristic Combined With β-amyloid Plaques

  • 摘要: 为研制新型99Tcm(CO)3+标记的黄酮类Aβ显像剂,设计合成了同型Re/99Tcm(CO)3+黄酮类衍生物,用荧光法研究了Re(CO)3+黄酮类衍生物在体外与Aβ斑块的结合特性,并初步观察了其在昆明小鼠体内的生物分布。结果表明,Re(CO)3+黄酮类衍生物的亲和常数(Kd=5.43 nmol/L)比放射性碘标记的黄酮类衍生物高。正常小鼠的动物分布结果表明,2 min内脑初始摄取较高(0.46±0.23 %ID/g),且清除较快(120 min时为0.13±0.04 %ID/g)。以上结果表明,99Tcm(CO)3+黄酮类衍生物有进一步研究的价值。

     

    Abstract: In vivo PET and SPECT imaging of β-amyloid (Aβ) plagques in the brain may lead to early detection of Alzheimer’s Disease (AD), but the Aβ-detector labeled by 99Tcm fell behind. The purpose of this study was to develop novel 99Tcm(CO)3+-labeled β-amyloid-detector based on the flavones. Isostructural Re/99Tcm(CO)3+-flavones were designed and synthesized, and Re(CO)3+-flavone were studied on its binding characteristic with βamyloid plaques in vitro by fluorescence. The results showed that the binding affinity(Kd=5.43 nmol/L) of Re(CO)3+-flavone was higher than flavone derivatives labeled by radioiodine. The biodistrubution of normal mice showed that 99Tcm(CO)3+-flavone displayed moderate uptake (0.46±0.23%ID/g) at 2 min postinjection) in the brain and rapid clearance (0.13±0.04%ID/g) after 120 min injection. The above results demonstrated that 99Tcm(CO)3+-flavone should be desirable as a potential SPECT imaging agent for β-amyloid aggregates.

     

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