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Selective contrast enhancement of individual Alzheimer's disease amyloid plaques using a polyamine and Gd-DOTA conjugated antibody fragment against fibrillar Abeta42 for magnetic resonance molecular imaging.

Abstract：

PURPOSE:The lack of an in vivo diagnostic test for AD has prompted the targeting of amyloid plaques with diagnostic imaging probes. We describe the development of a contrast agent (CA) for magnetic resonance microimaging that utilizes the F(ab')2 fragment of a monoclonal antibody raised against fibrillar human Abeta42 METHODS:This fragment is polyamine modified to enhance its BBB permeability and its ability to bind to amyloid plaques. It is also conjugated with a chelator and gadolinium for subsequent imaging of individual amyloid plaques RESULTS:Pharmacokinetic studies demonstrated this 125I-CA has higher BBB permeability and lower accumulation in the liver and kidney than F(ab')2 in WT mice. The CA retains its ability to bind Abeta40/42 monomers/fibrils and also binds to amyloid plaques in sections of AD mouse brain. Intravenous injection of 125I-CA into the AD mouse demonstrates targeting of amyloid plaques throughout the cortex/hippocampus as detected by emulsion autoradiography. Incubation of AD mouse brain slices in vitro with this CA resulted in selective enhancement on T1-weighted spin-echo images, which co-register with individual plaques observed on spatially matched T2-weighted spin-echo image CONCLUSIONS:Development of such a molecular probe is expected to open new avenues for the diagnosis of AD.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Ramakrishnan M,Wengenack TM,Kandimalla KK,Curran GL,Gilles EJ,Ramirez-Alvarado M,Lin J,Garwood M,Jack CR Jr,Poduslo JF

doi

10.1007/s11095-008-9600-9

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

1861-72

issue

8

eissn

0724-8741

issn

1573-904X

journal_volume

25

pub_type

杂志文章

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