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Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer’s disease (AD). We previously reported  99m Tc-hydroxamamide ( 99m Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1–42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging.  In vitro  inhibition assay using Aβ(1–40) aggregates deposited mainly in CAA and a brain uptake study were performed for  99m Tc-Ham complexes, and all  99m Tc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1–40) aggregates and very low brain uptake.  In vitro  autoradiography of human CAA brain sections and  ex vivo  autoradiography of Tg2576 mice were carried out for bivalent  99m Tc-Ham complexes ([ 99m Tc]SB2A and [ 99m Tc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the  99m Tc-Ham complex.

Imaging of Cerebral Amyloid Angiopathy with Bivalent 99mTc-Hydroxamamide Complexes