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Regular Article |
Received May 11, 2001; revised July 12, August 23, 2001; accepted September 6, 2001. From the Division of Nuclear Medicine, Department of Molecular and Medical Pharmacology, Laboratory of Structural Biology and Molecular Medicine; and Department of Psychiatry and Behavioral Sciences, Neuropsychiatric Institute, UCLA School of Medicine, Los Angeles, CA, and the Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia. Address correspondence to Jorge R. Barrio, Ph.D., Department of Molecular and Medical Pharmacology, B2-086A CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095-6948. e-mail: jbarrio{at}mednet.ucla.edu
The authors used 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP), a hydrophobic radiofluorinated derivative of 2-{1-[6-(dimethylamino)-2-naphthyl]ethylidene}malononitrile (DDNP), in conjunction with positron emission tomography to determine the localization and load of neurofibrillary tangles (NFTs) and ß-amyloid senile plaques (APs) in the brains of living Alzheimer disease (AD) patients. Previous work illustrated the in vitro binding characteristics of [18F]FDDNP to synthetic ß-amyloid(1-40) fibrils and to NFTs and APs in human AD brain specimens. In the present study, greater accumulation and slower clearance was observed in AP- and NFT-dense brain areas and correlated with lower memory performance scores. The relative residence time of the probe in brain regions affected by AD was significantly greater in patients with AD (n=9) than in control subjects (n=7; p=0.0007). This noninvasive technique for monitoring AP and NFT development is expected to facilitate diagnostic assessment of patients with AD and assist in response-monitoring during experimental treatments.
Key Words: Neuroimaging • PET • Alzheimer's Disease
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