99mTc(CO)3-Labeled Benzothiazole Derivatives Preferentially Bind Cerebrovascular Amyloid: Potential Use as Imaging Agents for Cerebral Amyloid Angiopathy

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.