Preparation of classical Re/99mTc(CO)3(+) and novel 99mTc(CO)2(NO)2+ cores complexed with flavonol derivatives and their binding characteristics for Abeta(1-40) aggregates.

摘要

Classical (99m)Tc(CO)(3)(+) and novel (99m)Tc(CO)(2)(NO)(2+) cores complexed with flavonol derivatives were prepared. Autoradiography of postmortem AD transgenic mice (Tg C57, APP, PS1 12-month-old) brain section confirmed the binding property of [(99m)Tc(CO)(3)(+)-3-OH-flavone](0) to Abeta((1-40)) aggregates, while the novel (99m)Tc(CO)(2)(NO)(2+) labeled compounds showed no binding sites in AD transgenic mice sections. Intravenous administration of [(99m)Tc(CO)(3)(+)-3-OH-flavone](0) resulted in moderate brain uptake (0.48+/-0.05%ID/g) at 5 min post-injection and slow clearance from the brain issues in 2h post-injection (120 min: 0.39+/-0.08%ID/g). Then an Abeta((1-40))-receptor-targeted Re(CO)(3)(+)-3-OH-flavone, was prepared to identify the structure of the technetium complex. UV-vis absorption and fluorescence emission properties have been studied at room temperature in order to determine the natures of the lowest electronically excited states of Re(CO)(3)(+)-3-OH-flavone and the ligand. The fluorescent rhenium complex Re(CO)(3)(+)-3-OH-flavone showed high affinity for Abeta((1-40)) aggregates in vitro by fluorescence spectra (dissociation constant (K(d))=11.16 nM). In conclusion, the results suggested that (99m)Tc(CO)(3)(+)-3-OH-flavone should be a suitable candidate as Abeta plaque SPECT imaging agent for AD.