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    Re/99Tcm(CO)3-EPBI与Aβ(1～40)结合能力的测定及生物分布

    Binding Affinity of Re(CO)3Cl(EPBI) for Aβ（1～40） Aggregates and Evaluation of 99Tcm(CO)3+-EPBI

      摘要
    • 摘要: 为发展锝-99m标记的阿尔茨海默病（Alzheimer’s disease, AD）早期诊断显像药物，在荧光测定法基础上，建立了体外荧光法测定羰基铼配合物与Aβ（1～40）淀粉样纤维结合的解离常数Kd的方法。同时，合成了配体2-(1-乙基苯并咪唑)吡啶（EPBI）及其铼的配合物Re(CO)3Cl(EPBI)，测定后者与体外缠结Aβ（1～40） 结合的解离常数Kd；采用直接标记法制备EPBI的99Tcm(CO)3+配合物，并研究配合物99Tcm (CO)3+-EPBI的理化性质及生物分布。结果表明，Re(CO)3Cl(EPBI)与Aβ（1～40）结合的解离常数Kd=13.3 μmol/L；正常小鼠体内生物分布研究表明，化合物99Tcm (CO)3+EPBI的脑初始（2 min内）摄取值为(0.63±0.17)%ID/g（n=3），在脑内清除较快，120 min时，摄取值为(0.27±0.03)%ID/g（n=3）。

       

      Abstract: The aim of this paper was to develop potential technetium 99m-labeled diagnostic imaging agents specific for the detection of Aβ plaques. Based on previously obtained Aβ plaque-specific biphenyls containing a benzimidazol group, 99Tcm and Re-benzimidazol derivatives, 99Tcm(CO)3+-EPBI and Re(CO)3Cl(EPBI), were prepared. The latter showed binding affinities towards Aβ（1～40） aggregates in vitro (Kd=13.3 μmol/L) by fluorophotometry. 2-(1-Ethylbenzimidazol-2-yl)pyridine（EPBI） and Re(CO)3Cl(EPBI) were synthesized. Binding affinity of Re(CO)3Cl(EPBI) for Aβ（1～40） aggregates was determined. 99Tcm(CO)3+-EPBI was prepared and analyzed by HPLC and paper eletrophoresis. Its biodistribution in mice was obtained. The Kd value of Re(CO)3Cl(EPBI) is 13.3 μmol/L. Biodistribution of 99Tcm(CO)3+-EPBI in mice shows brain penetration (0.63±0.17) %ID/g （n=3） at 2 min after iv injection in mice and rapid washout from normal brains (0.27±0.03) %ID/g （n=3） at 120 min. It may provide a new strategy to design the early diagnosis radiopharmaceuticals of AD labeled by 99Tcm(CO)3+ core according to the result.

       

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