Shoghi-Jadid Kooresh, Small Gary W, Agdeppa Eric D, Kepe Vladimir, Ercoli Linda M, Siddarth Prabha, Read Stephen, Satyamurthy Nagichettiar, Petric Andrej, Huang Sung-Cheng, Barrio Jorge R
Division of Nuclear Medicine, UCLA School of Medicine, Los Angeles, CA, USA.
Am J Geriatr Psychiatry. 2002 Jan-Feb;10(1):24-35.
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 beta-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 beta-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.
作者使用了2-(1-(6-[(2-[¹⁸F]氟乙基)(甲基)氨基]-2-萘基)亚乙基)丙二腈([¹⁸F]FDDNP)，它是2-(1-[6-(二甲氨基)-2-萘基]亚乙基)丙二腈(DDNP)的一种疏水性放射性氟化衍生物，结合正电子发射断层扫描来确定活体阿尔茨海默病(AD)患者大脑中神经原纤维缠结(NFTs)和β-淀粉样老年斑(APs)的定位和负荷。先前的研究表明了[¹⁸F]FDDNP在体外与合成的β-淀粉样蛋白(1-40)纤维以及人类AD脑标本中的NFTs和APs的结合特性。在本研究中，在AP和NFT密集的脑区观察到了更高的积聚和更慢的清除，并且与更低的记忆表现评分相关。与对照组(n = 7；p = 0.0007)相比，AD患者(n = 9)中探针在受AD影响的脑区的相对停留时间显著更长。这种监测AP和NFT发展的非侵入性技术有望促进AD患者的诊断评估，并有助于在实验性治疗期间进行反应监测。
