Binding Affinity of Re(CO)₃Cl(EPBI) for Aβ_（1～40） Aggregates and Evaluation of ⁹⁹Tc^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, ⁹⁹Tc^m and Re-benzimidazol derivatives, ⁹⁹Tc^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. ⁹⁹Tc^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 ⁹⁹Tc^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 ⁹⁹Tc^m(CO)₃⁺ core according to the result.