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

几年前，圣安德鲁斯实验室分离出一种非常不寻常的酶，因为它具有从无机氟离子形成碳-氟键的能力。这种酶被分离出来，并在大肠杆菌中鉴定和过表达的基因。这种酶已经成为一种非常有用的催化剂，用于将同位素F-18结合到有机分子中。使用其他酶与氟酶的组合，圣安德鲁斯实验室已经能够在适合于通过正电子发射断层扫描探索作为成像剂的产物的时间尺度（1-2小时）内制备几种新的氟-18标记的产物。我们已经开始与阿伯丁实验室合作，并有一些初步的数据表明，这些分子之一是积极运输到乳腺癌细胞，而且这些化合物之一可以适当地成像大鼠。这个学科跳跃补助金将使我们有机会结合联合收割机的实验室的专业知识，并确定是否可以将18 F-C键的氟酶介导的催化转移到临床热实验室环境中，并确定一些可以酶促制备的分子是否有潜力作为癌症（肿瘤学）和/成像大脑（神经学）的成像剂。

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).