Journal
MOLECULAR PHARMACEUTICS
Volume 12, Issue 8, Pages 2937-2946Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00209
Keywords
amyloid-beta; affinity; selectivity; CAA; autoradiography
Funding
- National Science and Technology Major Projects for Major New Drugs Innovation and Development [2014ZX09507007-002]
- National Natural Science Foundation of China [21201019]
- Beijing Municipal Natural Science Foundation [7143180]
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Cerebral amyloid angiopathy (CAA) is a disorder affecting the elderly that is characterized by amyloid-beta (A beta) deposition in blood vessel walls of the brain. A series of Tc-99m(CO)3-labeled benzothiazole derivatives as potential SPECT imaging probes for cerebrovascular A beta deposition is reported. Rhenium surrogate displayed high affinities to A beta aggregates with Ki values ranging from 106 to 42 nM, and they strongly stained A beta deposits in transgenic mice (Tg) and Alzheimers disease (AD) patients. In vitro autoradiography on brain sections of Tg and AD patients confirmed that [Tc-99m]24 possessed sufficient affinity for A beta plaques, and [Tc-99m]24 could only label A beta deposition in blood vessels but not A beta plaques in the parenchyma of the brain of AD patients. Moreover, [Tc-99m]24 possessed favorable initial uptake (1.21% ID/g) and fast blood washout (blood2 min/blood60 min = 23) in normal mice. These preliminary results suggest that [Tc-99m]24 may be used as an A beta imaging probe for the detection of CAA.
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