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EMISSION COMPUTED TOMOGRAPHY OF LOCAL CEREBRAL FUNCTION

局部脑功能的发射计算机断层扫描

基本信息

批准号：
6330433
负责人：
DAVID E KUHL
金额：
$ 43.19万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 2002-11-30
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from the applicant's abstract) The goals of this project are to determine, with in vivo emission tomography, the temporal and spatial sequence of declines in cerebral cholinergic enzyme activity and cholinergic terminal integrity in patients suspected of early Alzheimer s disease (AD) and in Parkinson s disease (PD), with and without dementia, and to correlate these neuronal biochemical alterations with associated cognitive declines. Hypotheses to be tested include: 1) in normal aging, AD, and PD, patterns differ, but cholinergic enzyme loss always precedes and exceeds cholinergic terminal loss both in severity and in extent; 2) in patients suspected of early AD, those with cholinergic enzyme deficits will progress to AD and those without enzyme deficits will not; and 3) patients with early AD who have the most severe temporal cholinergic deficits and occipital hypometabolism also have the premortem clinical criteria and neuro-psychological profile which have been attributed to Diffuse Lewy Body Disease (DLBD). These issues are difficult to establish with postmortem examinations due to the lack of tissue from early disease. Emission tomography studies using radioactive ligand markers of the presynaptic vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) substrate utilization are proposed in well characterized controls and patients. In parallel with these imaging studies, the development of a new AChE-inhibitor ligand is proposed. This agent will be evaluated in small animal and primate studies in preparation for radiotracer pharmacokinetic evaluation in humans. Success in these efforts is expected to aid the early differential diagnosis of dementing disorders and to provide new insights into the basic pathophysiology of these diseases. Such information could facilitate new pharmacologic classifications of patients, better matches of patients to therapies, more rational pathways to new drugs, and guides to new therapies and strategies for neuroprotection.

描述：（改编自申请人的摘要）本项目的目标

项目成果

期刊论文数量（77）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neurochemical imaging of Alzheimer's disease and other degenerative dementias.

阿尔茨海默病和其他退行性痴呆的神经化学成像。

DOI：
发表时间：
1998
期刊：
The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR)
影响因子：
0
作者：
Frey,KA;Minoshima,S;Kuhl,DE
通讯作者：
Kuhl,DE

Syntheses of carbon-11 labeled piperidine esters as potential in vivo substrates for acetylcholinesterase.

碳 11 标记哌啶酯的合成作为乙酰胆碱酯酶的潜在体内底物。

DOI：
10.1016/s0969-8051(98)00072-9
发表时间：
1998
期刊：
Nuclear medicine and biology
影响因子：
3.1
作者：
Nguyen,TB;Snyder,SE;Kilbourn,MR
通讯作者：
Kilbourn,MR

Cerebral glucose metabolic features of Parkinson disease and incident dementia: longitudinal study.

DOI：
10.2967/jnumed.111.089946
发表时间：
2011-06
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
0
作者：
Bohnen NI;Koeppe RA;Minoshima S;Giordani B;Albin RL;Frey KA;Kuhl DE
通讯作者：
Kuhl DE

An automated high pressure reaction vessel for routine preparation of short-lived radiopharmaceuticals.

用于常规制备短寿命放射性药物的自动化高压反应容器。

DOI：
10.1016/0883-2889(86)90046-8
发表时间：
1986
期刊：
International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes
影响因子：
0
作者：
Ropchan,JR;Ricci,AR;Low,GC;Phelps,ME;Barrio,JR
通讯作者：
Barrio,JR

The use of positron emission tomography in the clinical assessment of dementia.

正电子发射断层扫描在痴呆症临床评估中的应用。