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

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K_d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~(99)Tc~m(CO)_3]~+配合物,并研究配合物~(99)Tc~m (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K_d=13.3 μmol/L;正常小鼠体内生物分布研究表明,化合物~(99)Tc~m (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).

Binding Affinity of Re(CO)_3Cl(EPBI) for Aβ_(1～40) Aggregates and Evaluation of [~(99)Tc~m(CO)_3]~+-EPBI

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, ~(99)Tc~m and Re-benzimidazol derivatives, ~(99)Tc~m(CO)_3]~+-EPBI and Re(CO)_3Cl(EPBI), were prepared. The latter showed binding affinities towards Aβ_((1～40)) aggregates in vitro (K_d=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. ~(99)Tc~m(CO)_3]~+-EPBI was prepared and analyzed by HPLC and paper eletrophoresis. Its biodistribution in mice was obtained. The K_d value of Re(CO)_3Cl(EPBI) is 13.3 μmol/L. Biodistribution of ~(99)Tc~m(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 ~(99)Tc~m(CO)_3]~+ core according to the result.