TITLE

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

AUTHOR(S)
Dezutter, Nancy A.; Dom, René J.; de Groot, Tjibbe J.; Bormans, Guy M.; Verbruggen, Alfons M.
PUB. DATE
November 1999
SOURCE
European Journal of Nuclear Medicine;1999, Vol. 26 Issue 11, p1392
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Abstract. Chrysamine G (CG), an analogue of Congo red, is known to bind in vitro to the beta-amyloid protein (A beta 10-43) and to homogenates of several regions of the brain of Alzheimer's disease (AD) patients. We synthesised a conjugate of 2-(acetamido)-CG with a bis-S-trityl protected monoamide-monoaminedithiol (MAMA-Tr[sub 2]) tetraligand, which was efficiently deprotected and labelled with a 75% yield with technetium-99m, to obtain 99mTc-MAMA-CG. In mice, [sup 99m]Tc-MAMA-CG was cleared mainly by the hepatobiliary system, resulting in a fast blood clearance. Brain uptake of [sup 99m]Tc-MAMA-CG was low. Co-injection with the blood pool tracer iodine-125 human serum albumin ([sup 125]I-HSA) demonstrated a brain/blood activity ratio for [sup 99m]Tc-MAMA-CG that was significantly higher than that for [sup 125]I-HSA (t test for dependent samples, P<0.02), indicating the ability of [sup 99m]Tc-MAMA-CG to cross the blood-brain barrier. In vitro autoradiography demonstrated pronounced binding of [sup 99m]Tc-MAMA-CG to beta-amyloid deposits in autopsy sections of the parietal and occipital cortex of an AD patient as compared with controls. Adding 10 pM Congo red during incubation displaced the binding of [sup 99m]TcMAMA-CG. Congo red staining and autoradiography identified the same lesions. [sup 99m]Tc-MAMA-CG seems to bind selectively to beta-amyloid deposition in human brain parenchyma 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 Alzheimer's...
ACCESSION #
4721273

 

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