Transfer of fluorinase mediated C-18F bond formation technology to the clinical environment for tumor imaging by PET

将氟酶介导的 C-18F 键形成技术转移到临床环境中进行 PET 肿瘤成像

• 批准号: G0802567/1
• 负责人: Andy Welch
• 金额: $ 11.4万
• 依托单位: University of Aberdeen
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802567%2F1
• 关键词: Transfer; fluorinase; mediated; 18F; bond

Several years ago the St Andrews laboratory isolated a very unusual enzyme in that it had the ability to form carbon-fluorine bonds from inorganic fluoride ion. This enzyme was isolated and the gene identified and over-expressed in E.coli. The enzyme has emerged as an extremely useful catalyst for incorporating the isotope F-18 into an organic molecule. Using other enzymes in combination with the fluorinase enzyme the St Andrews laboratory have been able to make several novel fluorine-18 labelled products in time scales (1-2 hours) suitable for exploring the products as imaging agents, by positron emission tomography. We have begun to collaborate with the Aberdeen lab and have some preliminary data which shows that one of these molecules is actively transported into breast cancer cells, and also that one of these compounds can suitably image a rat. This Discipline Hopping grant will give us the opportunity to combine the expertise of the labs and establish if the fluorinase mediated catalysis of 18F-C bonds can be transferred into a clinical hot laboratory environment, and to establish if some of the molecules that can be prepared enzymatically have potential as imaging agents for cancer (oncology) and/ imaging the brain (neurology).

几年前，圣安德鲁斯实验室分离出一种非常不寻常的酶，它能够从无机氟离子中形成碳氟键。该酶在大肠杆菌中被分离、鉴定并过表达。这种酶已经成为一种非常有用的催化剂，可以将同位素F-18结合到有机分子中。使用其他酶与氟酶结合，圣安德鲁斯实验室已经能够在时间尺度上（1-2小时）制造出几种新的氟-18标记产品，适合通过正电子发射断层扫描探索这些产品作为显像剂。我们已经开始与阿伯丁实验室合作，并获得了一些初步数据，这些数据表明其中一种分子被积极地运送到乳腺癌细胞中，而且其中一种化合物可以适当地成像老鼠。这项学科跳跃资助将使我们有机会结合实验室的专业知识，并确定氟酶介导的18F-C键的催化作用是否可以转移到临床热实验室环境中，并确定一些可以用酶制备的分子是否有潜力作为癌症（肿瘤学）和脑成像（神经学）的显像剂。