ENZYME TARGETED IMAGING AGENTS FOR NEUROPSYCHIATRY

用于神经精神病学的酶靶向成像剂

• 批准号: 6309171
• 负责人: Onofre DeJesus
• 金额: $ 0.75万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-15 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6309171
• 关键词: Mammalia; bioimaging /biomedical imaging; biological products; biomedical resource; enzymes; human tissue; mental disorders; nervous system; positron emission tomography; radiology; technology /technique

This project involves developing imaging agents which will allow the asessment of dopaminergic and serotonergic activity in the brain non-invasively using positron emission tomography (PET). Short-lived positron emitting isotopes, 18F (t+=110 min.) and 11C (t+=20 min.), are introduced into amino acid analogs which are substrates of the rate limiting enzymes in the biosynthesis of dopamine and serotonin. Non-radioactive samples of these compounds are first sythesized and characterized by multinuclear NMR (1H, 11C, 19F). In addition, both the precursors and enzyme products of the desired compounds are prepared and characterized by NMR. These precursors and enzyme products are used in the synthesis of the desired compounds and their metabolic characterization, respectively. Radiolabeled compounds are then evaluated, in vitro and in vivo, as imaging agents for use in the study of neuropsychiatric disorders such as Parkinson's disease, affective disorders and depression.

该项目涉及开发成像剂， 脑中多巴胺能和多巴胺能活性的评估 使用正电子发射断层扫描（PET）非侵入性地进行。 短命 正电子发射同位素，18F（t+=110 min.）和11 C（t+=20 min）， 被引入到氨基酸类似物中，所述氨基酸类似物是 多巴胺和血清素生物合成中的限速酶。 首先合成这些化合物的非放射性样品， 通过多核NMR（1H，11C，19F）表征。 此外， 所需化合物的前体和酶产物 制备并通过NMR表征。 这些前体和酶 产物用于合成所需的化合物及其 代谢特征。 放射性标记的化合物是 然后在体外和体内评价，作为成像剂用于 神经精神疾病的研究，如帕金森氏病， 情感障碍和抑郁症。