title: 99mTc- and Re-labeled 6-dialkylamino-2-naphthylethylidene derivatives as imaging probes for β-amyloid plaques.
abstract: Based on the conjugate strategy, two neutral (99m)Tc labeled 2-(1-(6-(dialkylamino)naphthalen-2-yl)ethylidene)malononitrile (DDNP) and 1-(6-(dialkylamino)naphthalen-2-yl)ethanone (ENE) derivatives, and their corresponding rhenium complexes were synthesized. In vitro fluorescent staining indicated that the corresponding rhenium derivatives selectively stained the β-amyloid (Aβ) plaques in the brain sections of AD model mice with low background. Compared with FDDNP and FENE, the affinities of the corresponding rhenium derivatives to Aβ aggregates decreased about 10-14-fold. In vivo biodistribution experiments in normal mice showed that (99m)Tc-MAMA-ENE displayed medium initial brain uptake (0.65%ID/g at 2min) with a reasonable washout from the brain (0.19%ID/g at 2h) while (99m)Tc-MAMA-DDNP showed a low brain uptake (0.28%ID/g at 2 min). Further optimize these (99m)Tc-labeled tracers in order to improve their binding affinities to Aβ plaques and diffusion through the blood brain barrier may generate useful imaging agents for SPECT.
authors.affiliation: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, PR China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Ruikun
authors.initials: R
authors.lastname: Tang
authors.forename: Zijing
authors.initials: Z
authors.lastname: Li
authors.forename: Huiying
authors.initials: H
authors.lastname: Ren
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry*; D051379:Mice; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D016229:Amyloid beta-Peptides; D056831:Coordination Complexes; D009281:Naphthalenes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C031721:naphthalene; D012211:Rhenium