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In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer's disease patients.

Abstract：

PURPOSE:Imaging the 18-kDa translocator protein (TSPO) is considered a potential tool for in vivo evaluation of microglial activation and neuroinflammation in the early stages of Alzheimer's disease (AD). ((R)-1-(2-chlorophenyl)-N-[(11)C]-methyl-N-(1-methylpropyl)-3-isoquinoline caboxamide ([(11)C]-(R)-PK11195) has been widely used for PET imaging of TSPO and, despite its low specific-to-nondisplaceable binding ratio, increased TSPO binding has been shown in AD patients. The high-affinity radioligand N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoroethyl-5-methoxybenzyl)acetamide ([(18)F]FEDAA1106) has been developed as a potential in vivo imaging tool for better quantification of TSPO binding. The aim of this study was to quantify in vivo binding of [(18)F]FEDAA1106 to TSPO in control subjects and AD patients. METHODS:Seven controls (five men, two women, age 68±3 years, MMSE score 29±1) and nine AD patients (six men, three women, age 69±4 years, MMSE score 25±3) were studied with [(18)F]FEDAA1106. PET measurements were performed on an ECAT EXACT HR system (Siemens Medical Solutions) in two 60-min dynamic PET sessions with a 30-min interval between sessions. Arterial blood radioactivity was measured using an automated blood sampling system for the first 5 min and using manually drawn samples thereafter. Quantification was performed using both kinetic analysis based on a two-tissue compartment model and Logan graphical analysis. Outcome measures were total distribution volume (V T) and binding potential (BP(ND)=k3/k4). An estimate of nondisplaceable distribution volume was obtained with the Logan graphical analysis using the first 15 min of PET measurements (V(ND 1-15 min)). Binding potential (BP(ND)) was also calculated as: V(T)/V(ND 1-15 min) - 1. RESULTS:No statistically significant differences in V(T), k3/k4 or BP(ND) were observed between controls and AD patients. CONCLUSION:This study suggests that TSPO imaging with [(18)F]FEDAA1106 does not enable the detection of microglial activation in AD.

journal_name

Eur J Nucl Med Mol Imaging

journal_title

European journal of nuclear medicine and molecular imaging

authors

Varrone A,Mattsson P,Forsberg A,Takano A,Nag S,Gulyás B,Borg J,Boellaard R,Al-Tawil N,Eriksdotter M,Zimmermann T,Schultze-Mosgau M,Thiele A,Hoffmann A,Lammertsma AA,Halldin C

doi

10.1007/s00259-013-2359-1

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

921-31

issue

eissn

1619-7070

issn

1619-7089

journal_volume

pub_type

杂志文章

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In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer's disease patients.