PET Call: Development Of Quantitative CNS PET Imaging Probes For The Glutamate and GABA Systems

正电子发射断层扫描：临床中的反物质：今天，人们公认所有的亚原子粒子都有一面具有相反电荷和自旋的“镜子”或反物质对应物。我们对粒子和力的理解--宇宙的基本构件--是建立在这些对称性的基础上的，这些对称性自然地产生于强大的量子力学框架。正电子就是这样一个反物质粒子，它是电子的暗孪生粒子。1932年，加州理工学院的卡尔·安德森利用云室在宇宙射线中发现了它，并根据狄拉克方程预测了它的存在。反物质湮没提供了当今医院使用的主要成像技术之一。正电子发射断层扫描(PET)依赖于短命的正电子发射同位素(碳、氧、氮和氟)，这些同位素在被引入体内的选定药物中时充当示踪剂。一对180度角的伽马射线在正电子发射时被发射出来，一旦移动一小段距离(1毫米)，它们与组织接触时就会湮灭，并被周围的位置灵敏探测器阵列探测到(主要是高能物理和天文学研究的副产品)。这些信号被用来构建一系列贯穿人体的视觉“切片”，然后将这些切片组合成3D图像。使用PET扫描可以跟踪血液流动、肿瘤生长和药物在体内的作用等生物功能。它在对大脑结构和活动进行成像方面非常成功。尽管这些图像没有CT或磁共振成像(MRI)扫描的图像那么详细，但它们可以定量地测量生物分子的变化。PET扫描的改进使生理变化得以跟踪，例如阿尔茨海默病中发生的变化。PET还用于提供快速准确的肿瘤三维图像，以了解治疗反应并进行放射治疗计划。测量大脑：PET是一个蓬勃发展的领域，但也是一个非常复杂的领域；充分使用这项技术需要物理、放射化学、药理学、生物学和数学知识。英国大学已经迈出了很大的一步，培训人才，然后他们可以在这一领域的研究和工业中就业。这项提案希望将这一过程向前推进一步，为才华横溢的人提供综合培训，并使他们能够使用开发PET示踪剂所涉及的全部技术。为了实现这一点，我们专注于PET研究的一个特定领域，即开发可以测量大脑两种最重要的神经递质谷氨酸和GABA活性的PET放射性示踪剂。学员将有机会在独特的国际环境中进行培训和操作，并与学术界和工业界这一领域最优秀的研究人员互动。

Positron Emission Tomography: antimatter in the clinic:Today, it is accepted that all subatomic particles have a "mirror" or antimatter counterpart with opposite charge and spin. Our understanding of particles and forces - the fundamental building blocks of the Universe - is built on these kinds of symmetries, which arise naturally out of the powerful framework of quantum mechanics. The positron is one such antimatter particle being the dark twin of the electron. Predicted by Dirac's equations, its existence was confirmed when discovered in cosmic rays using a cloud chamber, in 1932 by Carl Anderson at the California Institute of Technology. Antimatter annihilation provides one of the main imaging techniques used in hospitals today. Positron emission tomography (PET) relies on short-lived positron-emitting isotopes (of carbon, oxygen, nitrogen and fluorine) which act as tracers when incorporated into selected pharmaceuticals introduced into the body. A pair of gamma-rays at 180 degree angle is emitted as the positrons emitted, once travelled a short distance (<1mm) annihilate as they come into contact with tissues and are detected by a surrounding position-sensitive detector array (largely developed as a spin-off from high-energy physics and astronomy research). The signals are used to construct a series of visual "slices" through the body that are then combined into a 3-D image. Biological functions such as blood flow, tumour growth and the action of drugs in the body can be followed using PET scans. It has been very successful at imaging brain structure and activity. Although the images are not as detailed as those from CT or magnetic resonance imaging (MRI) scans, they can measure biomolecular changes in a quantitative way. Improvements in PET scans have allowed physiological changes to be followed such as those that occur in Alzheimer's disease. PET is also used to provide fast and accurate 3-D images of tumours to see response to treatment and allow radiotherapy planning.Measuring the Brain:PET is a booming field but also a very complex one; full use of the technology requires knowledge of physics, radiochemistry, pharmacology, biology and mathematics. Large steps have been made by UK universities to train people that can then be employed in research and industry in this area. This proposal wants to move this process one step further, providing integrative training to brilliant minds and enable them to work through the whole array of technologies involved in the development of a PET tracer. To achieve this we focus on a particular area of PET research that is the development of PET radiotracers that can measure the activity of the two most important neurotransmitters of the brain, Glutamate and GABA. The trainees will have the opportunity to train and operate in a unique international environment and interact with the best researchers in this area in academia and industry.