PET AND SPECT IMAGING IN ALCOHOLIC SMOKERS

酗酒者的 PET 和 SPECT 成像

• 批准号: 2885016
• 负责人: JULIE K STALEY
• 金额: $ 12.61万
• 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/2885016
• 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 K 01申请请求支持，以促进候选人发展成为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的独立研究者。候选人提出的职业发展和研究计划将通过与Stephanie O 'Malley博士和Robert B Innis博士的持续指导关系来促进，Stephanie O' Malley博士和Robert Innis博士分别在酒精依赖的临床神经精神药理学和PET和SPECT成像方面具有国际公认的成就。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，最终领导一个独立和高效的药物依赖脑成像研究项目。该计划经过精心设计，以满足以下主要领域的特定职业发展需求：1）酒精中毒的临床研究方法; 2）人类放射性同位素的使用; 3）成像仪器和分析; 4）放射性示踪剂开发，药代动力学和示踪剂动力学建模;以及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研讨会、辅导、校外教学和研究等强化课程来实现。提出了三个具体目标，旨在评估主动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中关键多巴胺能和多巴胺能突触标志物的状态。我们建议：1）确定酗酒者的纹状体DA转运蛋白是否减少，并通过SPECT使用[123 I] β-CIT评估尼古丁在酗酒和非酗酒人群中的作用; 2）确定脑干5-HT转运蛋白是否在主动依赖性酗酒者中升高，并区分尼古丁在酒精和非酒精人群中的作用，如使用[123 I] β-CIT通过SPECT评估的，和3）如使用[18F]次阿坦色林通过PET评估的，确定皮质5 HT 2A受体在主动依赖性酒精吸烟者和酒精非吸烟者中是否受到差异调节。这些研究的结果将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毁灭性的大脑疾病。