title: 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.
abstract: 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.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Ruikun
authors.initials: R
authors.lastname: Tang
authors.forename: Huabei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D044948:Flavonols / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D012211:Rhenium / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D016229:Amyloid beta-Peptides; D044948:Flavonols; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012211:Rhenium