Abstract
Two uncharged 99mTc-labeled phenylbenzoxazole derivatives were biologically evaluated as potential imaging probes for β-amyloid plaques. The 99mTc and corresponding rhenium complexes were synthesized by coupling monoamine-monoamide dithiol (MAMA) and bis(aminoethanethiol) (BAT) chelating ligand via a pentyloxy spacer to phenylbenzoxazole. The fluorescent rhenium complexes 6 and 9 selectively stainined the β-amyloid plaques on the sections of transgenic mouse, and showed high affinity for Aβ (1-42) aggregates (K i = 11.1 nM and 14.3 nM, respectively). Autoradiography in vitro indicated that [ 99mTc]6 clearly labeled β-amyloid plaques on the sections of transgenic mouse. Biodistribution experiments in normal mice revealed that [ 99mTc]6 displayed moderate initial brain uptake (0.81% ID/g at 2 min), and quickly washed out from the brain (0.25% ID/g at 60 min). The preliminary results indicate that the properties of [ 99mTc]6 are promising, although additional refinements are needed to improve the ability to cross the blood-brain barrier.
Original language | English (US) |
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Pages (from-to) | 4327-4331 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 22 |
Issue number | 13 |
DOIs | |
State | Published - Jul 1 2012 |
Keywords
- β-Amyloid plaque
- Alzheimer's disease
- Imaging probe
- Phenylbenzoxazole
- Technetium-99m
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry