PET AND SPECT IMAGING IN ALCOHOLIC SMOKERS

酗酒者的 PET 和 SPECT 成像

• 批准号: 6371242
• 负责人: JULIE K STALEY
• 金额: $ 13.04万
• 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/6371242
• 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 申请请求支持，以促进候选人发展成为一名独立研究者，将正电子发射断层扫描 (PET) 和单光子发射断层扫描 (SPECT) 神经影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 是资深科学家，分别在酒精依赖的临床神经精神药理学以及 PET 和 SPECT 成像方面取得了国际公认的成就。全面的五年职业发展计划将为候选人提供最终领导独立且高效的物质依赖脑成像研究项目所需的多学科技能。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： l) 酗酒的临床研究方法； 2) 在人体中使用放射性同位素； 3）成像仪器与分析； 4) 放射性示踪剂开发、药代动力学和示踪动力学模型； 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，旨在评估主动依赖的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的多巴胺能和血清素能突触标记的状态。我们建议 l) 确定酗酒者中纹状体 DA 转运蛋白是否减少，并通过使用 [123I]beta-CIT 通过 SPECT 评估来描述尼古丁对酒精和非酒精人群的影响； 2) 确定主动依赖的酗酒者中脑干 5-HT 转运蛋白是否升高，并区分尼古丁对酒精和非酒精人群的影响，使用 [123I]beta-CIT 通过 SPECT 进行评估；3) 确定主动依赖的酒精吸烟者和酒精不吸烟者中皮质 5HT2A 受体是否受到差异性调节，使用 [18F]氘阿坦色林通过 PET 进行评估。这些研究的结果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，这可能会指导针对这些破坏性脑部疾病开发更有效的药物疗法。