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.
Pharm Res
; 25(8): 1861-72, 2008 Aug.
Article
em En
| MEDLINE
| ID: mdl-18443900
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 Abeta42METHODS:
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 plaquesRESULTS:
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 imageCONCLUSIONS:
Development of such a molecular probe is expected to open new avenues for the diagnosis of AD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Fragmentos de Peptídeos
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Poliaminas
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Peptídeos beta-Amiloides
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Meios de Contraste
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Placa Amiloide
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Doença de Alzheimer
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Compostos Heterocíclicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article