99mTc- and Re-labeled 6-dialkylamino-2-naphthylethylidene derivatives as imaging probes for β-amyloid plaques

✍ Scribed by Mengchao Cui; Ruikun Tang; Zijing Li; Huiying Ren; Boli Liu

• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 574 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.11.096

✦ Synopsis

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.