Tc-99m-MAMA-chrysamine G, a probe for beta-amyloid protein of Alzheimer's disease

Chrysamine G (CG), an analogue of Congo red, is known to bind in vitro to t he beta-amyloid protein (A beta 10-43) and to homogenates of several region s of the brain of Alzheimer's disease (AD) patients. We synthesised a conju gate of 2-(acetamido)-CG with a bis-S-trityl protected monoamide-monoamined ithiol (MAMA-Tr-2) tetraligland, which was efficiently deprotected and la b elled with a 75% yield with technetium-99m, to obtain Tc-99m-MAMA-CG. In mi ce, Tc-99m-MAMA-CG was cleared mainly by the hepatobiliary system, resultin g in a fast blood clearance. Brain uptake of Tc-99m-MAMA-CG was low. Co-inj ection with the blood pool tracer iodine-125 human serum albumin (I-125-HSA ) demonstrated a brain/blood activity ratio for Tc-99m-MAMA-CG that was sig nificantly higher than that for I-125-HSA (t test for dependent samples, P< 0.02), indicating the ability of 99mTc-MAMA-CG to cross the blood-brain bar rier. In vitro autoradiography demonstrated pronounced binding of Tc-99m-MA MA-CG to beta-amyloid deposits in autopsy sections of the parietal and occi pital cortex of an AD patient as compared with controls. Adding 10 mu M Con go red during incubation displaced the binding of Tc-99m-MAMA-CG. Congo red staining and autoradiography identified the same lesions. Tc-99m-MAMA-CG s eems to bind selectively to beta-amyloid deposition in human brain parenchy ma and blood vessels in vitro and thus might be a lead compound for further development of a useful tracer agent for the in vivo diagnosis of Alzheime r's disease.