MICA: [11C]BU99008 - A novel Positron Emission Tomography ligand for the Imidazoline2 Binding Site, First in human and initial patient group

MICA：[11C]BU99008 - 一种新型正电子发射断层扫描配体，用于咪唑啉 2 结合位点，首次出现在人类和初始患者组中

• 批准号: MR/L01307X/1
• 负责人: David Nutt
• 金额: $ 79.94万
• 依托单位: Imperial 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%2FL01307X%2F1
• 关键词: MICA; 11C; BU99008; novel; Positron

Illnesses that affect the brain such as dementias and depression cost the NHS and the country tens of billions of pounds each year and are a major cause of disability. There are other brain illnesses that are less common and less costly but are still very painful to the people that have them and their relatives, such as multiple sclerosis (MS) and brain tumours. One of the things these illnesses have in common is inflammation within the brain. If we were able to measure this inflammation in living humans, it would enable us better to diagnose these illnesses at an early stage when we have the best chance to cure or slow down their development. Being able to measure this inflammation will also enable us to monitor and understand these illnesses better, and any potential treatments. The purpose of this work is to develop a way of measuring this inflammation in an early stage of dementia called Mild Cognitive Impairment, or MCI. MCI is an early stage of different types of dementia such as Alzheimer's Disease. The way we intend to do this is to use a very powerful technique for visualising inside humans, called positron emission tomography, or PET. PET relies on specially designed radioactive chemicals that provide a means to visualise what is happening in the brain. Therefore, we plan to develop such a radioactive chemical for a protein called the imidazoline2 binding site. This protein is found in a type of brain cell called glial. These cells are a normal part of the brain. However, in the illnesses where the brain is damaged and inflammation exists, there are more of these cells, especially in the inflamed areas. We already know that the amount of this protein is increased in the brains of people who have died of these diseases such as Alzheimer's Disease. If we can measure a change in this protein in living patients it will mean we have a way of measuring this brain inflammation found in this and similar illnesses, early on giving the sufferer the best chance of treatment.

痴呆症和抑郁症等影响大脑的疾病每年花费NHS和国家数百亿英镑，是导致残疾的主要原因。还有其他不太常见、成本更低的脑部疾病，但对患有这些疾病的人及其亲属来说仍然非常痛苦，如多发性硬化症(MS)和脑瘤。这些疾病的共同之处之一是大脑内的炎症。如果我们能够测量活人的这种炎症，将使我们能够更好地在早期诊断这些疾病，那时我们有最好的机会治愈或减缓它们的发展。能够测量这种炎症也将使我们能够更好地监测和了解这些疾病，以及任何潜在的治疗方法。这项工作的目的是开发一种方法，在痴呆症的早期阶段测量这种炎症，称为轻度认知障碍，或MCI。MCI是阿尔茨海默病等不同类型痴呆症的早期阶段。我们打算这样做的方法是使用一种非常强大的技术来可视化人体内部，称为正电子发射断层扫描，或PET。宠物依赖于特殊设计的放射性化学物质，这些化学物质提供了一种可视化大脑中正在发生的事情的方法。因此，我们计划为一种称为咪唑啉2结合位点的蛋白质开发这样一种放射性化学物质。这种蛋白质存在于一种叫做胶质细胞的脑细胞中。这些细胞是大脑的正常部分。然而，在大脑受损和存在炎症的疾病中，这些细胞更多，特别是在发炎的区域。我们已经知道，在死于阿尔茨海默病等疾病的人的大脑中，这种蛋白质的数量会增加。如果我们能够在活着的患者身上测量这种蛋白质的变化，这将意味着我们有一种方法来测量在这种疾病和类似疾病中发现的这种脑部炎症，从而在早期为患者提供最好的治疗机会。

项目成果

Imidazoline 2 binding sites reflecting astroglia pathology in Parkinson's disease: an in vivo11C-BU99008 PET study.

• DOI: 10.1093/brain/awz260
• 发表时间: 2019-08
• 期刊: Brain : a journal of neurology
• 作者: H. Wilson;G. Dervenoulas;G. Pagano;R. Tyacke;Sotirios Polychronis;J. Myers;R. Gunn;E. Rabiner;D. Nutt;M. Politis

The entropic tongue: Disorganization of natural language under LSD.

熵舌：LSD 下自然语言的混乱。

• DOI: 10.1016/j.concog.2020.103070
• 发表时间: 2021
• 期刊: Consciousness and cognition
• 影响因子: 2.4
• 作者: Sanz C