Highlights of PET studies on chiral radiotracers and drugs at Brookhaven
Highlights of PET studies on chiral radiotracers and drugs at Brookhaven
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DOI：
10.1002/ddr.10221
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发表时间：
2003-06-01
影响因子：
3.8
通讯作者：
Fowler, JS
中科院分区：
文献类型：
--
作者：
Ding, YS;Fowler, JS
我们回顾了我们实验室进行的几项手性分子 PET 研究。在许多情况下，对映体表现不同，反映了诸如酶和转运蛋白的差异特异性、与血浆蛋白的结合以及与受体的选择性结合等因素。这些研究表明，PET 成像是研究手性药物在人体内行为的合适方法，也是药物开发的有力工具。重要的是要强调有机合成在过去四分之一个世纪中在 PET 发展中所发挥的重要和关键作用。 PET 现在已成为神经科学、心脏病学和肿瘤学领域的重要工具，并在全球数百家机构中使用。然而，PET在手性药物的研究方面还远未成熟；数百种外消旋药物已被开发出来，但只有少数被用正电子发射体标记以研究其立体选择性。原因之一是快速合成的复杂性，包括手性合成和手性纯化。这些领域需要新的发展。尽管 PET 是一项具有挑战性且昂贵的技术，但它非常适合人脑和其他器官的功能和神经化学研究。它在药物研究和开发中的应用有望了解药物的作用持续时间和立体选择性，并促进药物发现和将新药引入医学实践。 (C) 2003 Wiley-Liss, Inc.
We review several PET studies of chiral molecules which have been carried out in our laboratory. In many cases the enantiomers behave differently, reflecting factors such as differential specificity for enzymes and transporters and binding to plasma proteins, as well as selective binding to receptors. These studies demonstrate that PET imaging is a suitable method to investigate the behavior of a chiral drug in the human body and is a powerful tool in drug development. It is important to emphasize the essential and pivotal role that organic synthesis has played in the development of PET during the last quarter century. PET is now an important tool in the neurosciences, cardiology, and oncology and is available in hundreds of institutions worldwide. However, PET is by no means mature in terms of the study of chiral drugs; hundreds of racemic drugs have been developed but only a few have been labeled with positron emitters to study their stereoselectivity. One reason is the complexity of rapid synthesis, including chiral synthesis and chiral purification. New developments in these areas are needed. Although PET is a challenging and expensive technology, it is exquisitely suited to functional and neurochemical studies of the human brain and other organs. its use in drug research and development holds promise in understanding duration of action and stereoselectivity of drugs and in facilitating drug discovery and the introduction of new drugs into the practice of medicine. (C) 2003 Wiley-Liss, Inc.