DAT Binding by Pet in Adult ADHD

成人 ADHD 中宠物的 DAT 结合

• 批准号: 7017092
• 负责人: Thomas J Spencer
• 金额: $ 54.45万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-24 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017092
• 关键词: age difference; attention deficit disorder; bioimaging /biomedical imaging; clinical research; comorbidity; dopamine transporter; functional ability; gender difference; genetic susceptibility; human middle age (35-64); human subject; interpersonal relations; interview; iodine; mental disorders; molecular genetics; neurobiology; neuropsychological tests; neuropsychology; patient oriented research; positron emission tomography; protein binding; radionuclides; young adult human (21-34)

DESCRIPTION (provided by applicant): This is the second resubmission of an R01 application. We recently measured dopamine transporter (DAT) binding in adults with ADHD, using single photon emission computed tomography (SPECT) with the highly selective radiopharmaceutical, altropane.[9] DAT binding in was 70% greater Jn adults with ADHD. Our findings were partially replicated by Krause et al., (17% increase) but not replicated by van Dyck et al. (no increase), both using less specific radioligands. Positron emission tomography (PET) with 11C- altropane is ideal to measure DAT. It produces higher resolution, improved signal-to-noise ratio and less artifact than SPECT over a shorter acquisition time and permits kinetic modeling and estimates of affinity and density. To date, 6 adults and 6 controls have been imaged at MGH using [11C]altropane and PET which revealed a 34% increase in DAT binding. Moreover, Cook and others have demonstrated an association between ADHD and the 480-bp allele of the dopamine transporter gone. To this end, the primary goal of this molecular imaging proposal is to firmly establish the magnitude of increased DAT binding in adult ADHD with expert diagnostic methodology, a much larger N (66), a technically superior ligand (11C- altropane) and state-of-the-art imaging (PET). In addition, we seek to extend the previous findings to examine density (B'max) and affinity (Kd). The proposed work should move the field of ADHD research into a new direction in which molecular genetic and imaging studies are combined. Our specific aims are the following: 1. To examine DAT receptor bindinq in adults with ADHD usinq PET scanninq with 11C altropane as the li.qand. We hypothesize that compared to adults without ADHD, adults with ADHD will have greater DAT binding that will not be accounted for by psychiatric comorbidity, gender or age. Furthermore, we will separately examine density of DAT sites and affinity. 2. To examine the relationship of DAT binding to clinical features of ADHD. We hypothesize that DAT binding will be positively correlated with a) severity of ADHD symptoms; and b) neuropsychological and interpersonal dysfunction. 3. To examine the relationship between DAT bindinq and .qenetic risk factors, a) We hypothesize that DAT binding will be associated with the 480 allele of the 40-bp VNTR in the 3'-untranslated region of the dopamine transporter gene.

描述（由申请人提供）：这是R01申请的第二个重新提交。 我们最近使用具有高度选择性的放射性药物，易体烷的单个光子发射计算机断层扫描（SPECT）测量了ADHD成年人的多巴胺转运蛋白（DAT）结合。[9] DAT结合在患有多动症的JN成年人中增加了70％。我们的发现部分由Krause等人部分复制（增加17％），但未由Van Dyck等人复制。 （无增加），均使用较少的特异性放射线。 具有11C-易曲（PET）的正电子发射断层扫描（PET）是测量DAT的理想选择。与SPECT相比，在较短的采集时间中，它产生更高的分辨率，提高了信噪比和伪像较少，并允许动力学建模和亲和力和密度的估计。迄今为止，使用[11C]易曲（PET）和PET在MGH上成像了6个成人和6个对照，揭示了DAT结合的34％。此外，库克和其他人表现出多巴胺转运蛋白的480 bp等位基因之间的关联。 为此，该分子成像提案的主要目标是通过专家诊断方法，较大的N（66），技术上优越的配体（11C-易经）和状态 - 艺术成像（宠物）。此外，我们试图扩展先前的发现以检查密度（B'Max）和亲和力（KD）。拟议的工作应将多动症研究领域转移到一个新的方向，其中分子遗传和成像研究合并。我们的具体目的是：1。检查具有ADHD USINQ PET SCANNINQ成年人的DAT受体Bindinq，并以11C偏心烷为Li.Qand。我们假设，与没有多动症的成年人相比，患有多动症的成年人将具有更大的DAT结合，而精神病合并症，性别或年龄将无法解释。此外，我们将分别检查DAT位点和亲和力的密度。 2。检查DAT结合与多动症的临床特征的关系。我们假设DAT结合将与A）ADHD症状的严重程度正相关； b）神经心理学和人际功能障碍。 3。为了检查Dat Bindinq和.qenetic危险因素之间的关系，a）我们假设DAT结合将与多巴胺转运蛋白基因的3'-非翻译区域中40 bp VNTR的480等位基因相关。