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

Classical 99mTc(CO)3+ and novel 99mTc(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 [99mTc(CO)3+-3-OH-flavone]0 to Aβ(1–40) aggregates, while the novel 99mTc(CO)2(NO)2+ labeled compounds showed no binding sites in AD transgenic mice sections. Intravenous administration of [99mTc(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 2 h post-injection (120 min: 0.39 ± 0.08%ID/g). Then an Aβ(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 Aβ(1–40) aggregates in vitro by fluorescence spectra (dissociation constant (Kd) = 11.16 nM). In conclusion, the results suggested that 99mTc(CO)3+-3-OH-flavone should be a suitable candidate as Aβ plaque SPECT imaging agent for AD.

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