PET Imaging agents for a4b2 Nicotinic Receptors

a4b2 烟碱受体 PET 显像剂

• 批准号: 10060568
• 负责人: Bradley T Christian
• 金额: $ 24.91万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10060568
• 关键词: Affinity; Age; Aging; Agonist; Alzheimer' s Disease; Alzheimer' s disease brain; Anterior; Applications Grants; Area; Autopsy; Autoradiography; Binding; Bladder; Brain; Brain Diseases; Brain region; California; Cognition; Corpus Callosum; Development; Diagnosis; Disease; Disease model; Evaluation; Female; Fluorescent Probes; Functional disorder; Funding; Gender; Goals; Grouping; Hippocampus (Brain); Human; Image; Injections; Internal Capsule; Knock-out; Knockout Mice; Learning; Malignant neoplasm of lung; Measures; Memory; Methods; Mus; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Nicotine Dependence; Nicotinic Receptors; Organ; Outcome; Parkinson Disease; Physiological; Play; Positron-Emission Tomography; Radiometry; Role; Scanning; Schizophrenia; Slice; Testing; Thalamic structure; Tobacco Dependence; Translations; Universities; Wild Type Mouse; Wisconsin; age effect; age group; age related; base; cognitive enhancement; cognitive function; design; frontal lobe; gender difference; human imaging; human study; human subject; imaging agent; imaging modality; lung cancer screening; male; mouse model; programs; putamen; receptor; receptor function; thalamocortical tract; therapeutic development; translational study; treatment planning; white matter

Project Summary Nicotinic 42* receptors have been implicated in a number of pathophysiologies. At University of California- Irvine (UCI) and University of Wisconsin-Madison (UWM), we have several major programs that would gain from imaging nicotinic receptors. These include: 1) Program in aging and neurodegenerative disorders; 2) Program on studies related to nicotine dependence; 3) Program in the early detection of lung cancer, and 4) Neurobiology of learning and memory. During the previous 3-year funding period we have successfully completed initial human PET studies (test-retest and radiation dosimetry) with [18F]Nifene with the following outcomes: 1) [18F]Nifene requires a 40 min dynamic scan for quantitation; 2) Urinary bladder is the critical organ, and 4 PET studies with 5 mCi injections can be done annually; 3) Nifene measures 42, 32 and 22 receptor subtypes; 4) Nifene is a partial agonist; 5) [18F]Nifene is able to detect thalamic radiations (white matter tracts); 6) Females show greater [18F]Nifene binding than males; and 7) No aging effect on [18F]Nifene binding was observed. Since the initial study included only 8 subjects, a larger group of subjects is required in order to confirm the findings of male-female differences and aging using [18F]Nifene. In this 3-year renewal application our goals are: 1) Confirm male-female differences using 32 healthy subjects (16M, 16F) and examine aging effects by grouping 16 (8M, 8F) in their 20’s and 16 (8M, 8F) in their 70’s in all brain regions. 2) In the second goal, in pursuit of translation of [18F]Nifene PET to study human neurodegeneration, we propose to study postmortem brains of Alzheimer’s disease (AD) and Parkinson’s disease (PD). Two brain areas have been chosen based on previous findings of their significance, anterior cingulate (with corpus callosum) and hippocampus (containing CA1/subiculum). These will be evaluated using [18F]Nifene in 3 groups: controls, AD and PD (32 subjects in each group, 16M, 16F). 3) The third goal is to evaluate degree of binding of [18F]Nifene to the receptor subtypes using knock-out (KO) mice. Both 2 and 4 KO will be studied using [18F]Nifene PET and autoradiography and a male-female and aging effect will be evaluated in wild-type (WT) mice. This renewal application will help to ascertain that females have greater levels of [18F]Nifene binding (greater availability of 42* receptors), there is no aging effect on [18F]Nifene binding and whether there is a change in 42* receptors in neurodegeneration in certain brain regions. Additionally, the mice studies using [18F]Nifene will provide information on receptor selectivity and similarities with humans in terms of gender effects and aging. These studies will be important and necessary to carry translational studies in neurodegeneration, both mice models and humans.

项目总结

项目成果

Targeting histone deacetylase in lung cancer for early diagnosis: (18)F-FAHA PET/CT imaging of NNK-treated A/J mice model.

针对肺癌中的组蛋白脱乙酰酶进行早期诊断：(18)NNK 治疗的 A/J 小鼠模型的 F-FAHA PET/CT 成像。

• 发表时间: 2014
• 期刊: American journal of nuclear medicine and molecular imaging
• 影响因子: 2.5
• 作者: Tang,Wayland;Kuruvilla,SharonA;Galitovskiy,Valentin;Pan,Min-Liang;Grando,SergeiA;Mukherjee,Jogeshwar
• 通讯作者: Mukherjee,Jogeshwar

Elevated Monoamine Oxidase-A in Anterior Cingulate of Post-Mortem Human Parkinson's Disease: A Potential Surrogate Biomarker for Lewy Bodies?

• DOI: 10.3390/cells11244000
• 发表时间: 2022-12-10
• 期刊: Cells
• 影响因子: 6

Synthesis and evaluation of (S)-[(18)F]fesetron in the rat brain as a potential PET imaging agent for serotonin 5-HT3 receptors.

(S)-[(18)F]fesetron 在大鼠大脑中的合成和评估，作为血清素 5-HT3 受体的潜在 PET 成像剂。

• DOI: 10.1016/j.bmcl.2016.03.018
• 发表时间: 2016
• 期刊: Bioorganic & medicinal chemistry letters
• 影响因子: 2.7
• 作者: Pithia,NeemaK;Liang,Christopher;Pan,Xiang-Zuo;Pan,Min-Liang;Mukherjee,Jogeshwar
• 通讯作者: Mukherjee,Jogeshwar

Evaluation of F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging.

• DOI: 10.1186/2191-219x-1-6
• 发表时间: 2011-06-01
• 期刊: EJNMMI research
• 影响因子: 3.2
• 作者: Kant R;Constantinescu CC;Parekh P;Pandey SK;Pan ML;Easwaramoorthy B;Mukherjee J
• 通讯作者: Mukherjee J

Development of fluorescence imaging probes for nicotinic acetylcholine α4β2∗ receptors.

烟碱乙酰胆碱α4β2β受体荧光成像探针的开发。

• DOI: 10.1016/j.bmcl.2017.12.036
• 发表时间: 2018
• 期刊: Bioorganic & medicinal chemistry letters
• 影响因子: 2.7
• 作者: Samra,GurleenK;Intskirveli,Irakli;Govind,AnithaP;Liang,Christopher;Lazar,Ronit;Green,WilliamN;Metherate,Raju;Mukherjee,Jogeshwar
• 通讯作者: Mukherjee,Jogeshwar