Dopamine Transporter Binding by PET in Adult ADHD

成人 ADHD 中 PET 与多巴胺转运蛋白的结合

• 批准号: 6612445
• 负责人: Thomas J Spencer
• 金额: $ 57.07万
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612445
• 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R 01申请的第二次重新提交。 我们最近测量了多巴胺转运蛋白（DAT）结合在成人多动症，使用单光子发射计算机断层扫描（SPECT）与高选择性放射性药物，阿托烷。[9]DAT结合率比ADHD成人高70%。Krause等人部分重复了我们的发现，(17%增加），但货车Dyck等人未重复（无增加），两者均使用较低特异性的放射性配体。 正电子发射断层扫描（PET）与11 C- altropane是理想的测量DAT。它产生更高的分辨率，改善信噪比和更少的伪影比SPECT在较短的采集时间，并允许动力学建模和亲和力和密度的估计。迄今为止，6名成人和6名对照已在MGH使用[11 C]阿托烷和PET成像，显示DAT结合增加了34%。此外，库克和其他人已经证明了ADHD和多巴胺转运蛋白480 bp等位基因的缺失之间的关联。 为此，该分子成像提案的主要目标是通过专家诊断方法、更大的N（66）、技术上更上级的配体（11 C-阿托烷）和最先进的成像（PET），牢固地建立成人ADHD中DAT结合增加的幅度。此外，我们试图扩展以前的研究结果，以检查密度（B 'max）和亲和力（Kd）。这项工作将把ADHD研究领域推向一个新的方向，将分子遗传学和影像学研究结合起来。我们的具体目标如下：1.目的：用11 C阿托烷为脂质体的PET显像，检测成人ADHD患者DAT受体结合。我们假设，与没有ADHD的成年人相比，患有ADHD的成年人将具有更大的DAT结合，而精神科合并症，性别或年龄并不占优势。此外，我们将分别检查DAT位点的密度和亲和力。 2.研究DAT结合与ADHD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;和B）神经心理和人际功能障碍正相关。 3.为了检验DAT结合与遗传风险因素之间的关系，a）我们假设DAT结合与多巴胺转运蛋白基因3 '非翻译区中40-bp VNTR的480等位基因相关。