PET AND SPECT IMAGING IN ALCOHOLIC SMOKERS

酗酒者的 PET 和 SPECT 成像

• 批准号: 6532342
• 负责人: JULIE K STALEY
• 金额: $ 13.27万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532342
• 关键词: alcoholism /alcohol abuse; bioimaging /biomedical imaging; biomarker; brain stem; clinical research; comorbidity; dopamine transporter; human subject; iodine; magnetic resonance imaging; neurochemistry; nicotine; positron emission tomography; radionuclides; radiotracer; serotonin receptor; serotonin transporter; single photon emission computed tomography; smoking

This MRSDA K0l application requests support to promote the candidate's development into an independent investigator in the application of positron emission tomography (PET) and single photon emission tomography (SPECT) neuroimaging methods to the neurochemistry of alcohol and nicotine dependence. The candidate's proposed Career Development and Research Plans will be facilitated by ongoing mentoring relationships with Drs. Stephanie O'Malley and Robert B Innis, established senior scientists with internationally recognized accomplishments in clinical neuropsychopharmacology of alcohol dependence and PET and SPECT imaging, respectively. A comprehensive five-year Career Development Plan will provide the candidate with the multi- disciplinary skills required to ultimately lead an independent and highly productive research program in brain imaging of substance dependence. This plan has been carefully devised to satisfy specific career development needs in the following major areas: l) clinical research methods in alcoholism; 2) use of radioisotopes in humans; 3) imaging instrumentation and analysis; 4) radiotracer development, pharmacokinetic and tracer kinetic modeling; and 5) quantitative skills and biostatistics. Formal training in these highly specialized areas will be achieved through an intensive curriculum of seminars, tutorials, extramural didactics, and research studies. Three specific aims are proposed which seek to assess the status of key dopaminergic and serotonergic synaptic markers in actively dependent alcoholic smokers and nonsmokers and nonalcoholic smokers and nonsmokers. We propose l) to determine if striatal DA transporters are decreased in alcoholics and to delineate the effects of nicotine in the alcoholic and nonalcoholic populations as assessed via SPECT using [123I]beta-CIT; 2) To determine if brainstem 5-HT transporters are elevated in actively dependent alcoholics and to distinguish the effects of nicotine in alcoholic and nonalcoholic populations, as assessed via SPECT using [123I]beta-CIT and 3) To determine if cortical 5HT2A receptors are differentially regulated in actively dependent alcoholic smokers and alcoholic nonsmokers as assessed via PET using [18F]deuteroaltanserin. The findings from these studies will offer insight into the neurochemical alterations associated with dual alcohol and nicotine dependence which may guide the development of more effective pharmacotherapies for these devastating brain disorders.

该MRSDA K0l申请要求支持候选人发展成为一名独立的研究者，将正电子发射断层扫描（PET）和单光子发射断层扫描（SPECT）神经成像方法应用于酒精和尼古丁依赖的神经化学。候选人提出的职业发展和研究计划将通过与博士的持续指导关系得到促进。Stephanie O'Malley和Robert B Innis，分别在酒精依赖的临床神经精神药理学和PET和SPECT成像方面取得了国际公认的成就。一个全面的五年职业发展计划将为候选人提供所需的多学科技能，最终领导一个独立的和高效的研究项目在物质依赖的脑成像。该计划经过精心设计，以满足下列主要领域的具体职业发展需要：1)酗酒的临床研究方法；2)放射性同位素在人类中的使用；3)成像仪器与分析；4)放射性示踪剂研制、药代动力学及示踪剂动力学建模；5)定量技能和生物统计学。这些高度专业化领域的正式培训将通过密集的研讨会、辅导、校外教学和研究课程来实现。提出了三个具体目标，旨在评估积极依赖酒精吸烟者和非吸烟者以及非酒精吸烟者和非吸烟者的关键多巴胺能和血清素能突触标志物的状态。我们建议1)确定纹状体DA转运体是否在酗酒者中减少，并通过SPECT使用[123I] β - cit评估尼古丁对酗酒者和非酗酒者的影响；2)确定脑干5-羟色胺转运体是否在积极依赖酒精者中升高，并区分尼古丁对酒精和非酒精人群的影响，通过SPECT使用[123I] β - cit进行评估；3)通过PET使用[18F]deuteroaltanserin进行评估，确定皮质5HT2A受体在积极依赖酒精吸烟者和酒精非吸烟者中是否有差异调节。这些研究的发现将有助于深入了解与酒精和尼古丁双重依赖相关的神经化学变化，这可能会指导开发更有效的药物治疗这些破坏性的脑部疾病。