^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-β (Aβ) deposition in blood vessel walls of the brain. A series of ^99mTc­(CO)₃-labeled benzothiazole derivatives as potential SPECT imaging probes for cerebrovascular Aβ deposition is reported. Rhenium surrogate displayed high affinities to Aβ aggregates with <i>K</i>_i values ranging from 106 to 42 nM, and they strongly stained Aβ deposits in transgenic mice (Tg) and Alzheimer’s disease (AD) patients. In vitro autoradiography on brain sections of Tg and AD patients confirmed that [^99mTc]<b>24</b> possessed sufficient affinity for Aβ plaques, and [^99mTc]<b>24</b> could only label Aβ deposition in blood vessels but not Aβ plaques in the parenchyma of the brain of AD patients. Moreover, [^99mTc]<b>24</b> possessed favorable initial uptake (1.21% ID/g) and fast blood washout (blood_{2 min}/blood_{60 min} = 23) in normal mice. These preliminary results suggest that [^99mTc]<b>24</b> may be used as an Aβ imaging probe for the detection of CAA