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

PET 征集：开发用于谷氨酸和 GABA 系统的定量 CNS PET 成像探针

• 批准号: MR/K022733/1
• 负责人: Federico Turkheimer
• 金额: $ 123.24万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK022733%2F1
• 关键词: PET; Call; Development; Quantitative; CNS

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.

正电子发射断层扫描：临床中的反物质：今天，人们接受所有亚原子粒子都有一个“镜像”或反物质，具有相反的电荷和自旋。我们对粒子和力--宇宙的基本组成部分--的理解是建立在这些对称性的基础上的，这些对称性是从量子力学的强大框架中自然产生的。正电子是一种反物质粒子，它是电子的暗孪生子。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正电子，从而证实了正电子的存在。反物质湮灭是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）依赖于短寿命的正电子发射同位素（碳，氧，氮和氟），这些同位素在掺入引入体内的选定药物时充当示踪剂。一对180度角的伽马射线随着正电子的发射而发射，一旦传播了很短的距离（<1毫米），当它们与组织接触时就会湮灭，并被周围的位置敏感探测器阵列检测到（主要是作为高能物理和天文学研究的副产品开发的）。这些信号被用来构建一系列穿过身体的视觉“切片”，然后组合成3D图像。生物功能，如血流，肿瘤生长和药物在体内的作用可以使用PET扫描。它在成像大脑结构和活动方面非常成功。虽然这些图像不如CT或磁共振成像（MRI）扫描的图像详细，但它们可以定量地测量生物分子的变化。PET扫描的改进使得人们可以跟踪生理变化，例如阿尔茨海默病中发生的变化。PET还可用于提供快速准确的肿瘤三维图像，以了解治疗反应并制定放射治疗计划。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;充分利用该技术需要物理学、放射化学、药理学、生物学和数学知识。英国大学已经采取了重大步骤，培养可以在该领域的研究和工业中就业的人才。该提案希望将这一过程进一步推进，为杰出的头脑提供综合培训，使他们能够通过PET示踪剂开发中涉及的整个技术阵列进行工作。为了实现这一目标，我们专注于PET研究的一个特定领域，即PET放射性示踪剂的开发，该示踪剂可以测量大脑中两种最重要的神经递质谷氨酸和GABA的活性。学员将有机会在独特的国际环境中进行培训和运作，并与学术界和工业界在这一领域的最佳研究人员进行互动。

项目成果

Imaging niacin trafficking with positron emission tomography reveals in vivo monocarboxylate transporter distribution.

• DOI: 10.1016/j.nucmedbio.2020.07.002
• 发表时间: 2020-09
• 期刊: Nuclear medicine and biology
• 影响因子: 3.1
• 作者: Bongarzone S;Barbon E;Ferocino A;Alsulaimani L;Dunn J;Kim J;Sunassee K;Gee A
• 通讯作者: Gee A

Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors.

• DOI: 10.1038/s41598-017-14203-4
• 发表时间: 2017-11-03
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Bhattacharyya S;Egerton A;Kim E;Rosso L;Riano Barros D;Hammers A;Brammer M;Turkheimer FE;Howes OD;McGuire P
• 通讯作者: McGuire P