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

影响大脑的疾病，如痴呆症和抑郁症，每年花费NHS和国家数百亿英镑，是残疾的主要原因。还有其他脑部疾病不太常见，费用也不太高，但对患者及其亲属来说仍然非常痛苦，如多发性硬化症（MS）和脑瘤。这些疾病的共同点之一是大脑内的炎症。如果我们能够测量活体人类的这种炎症，它将使我们能够更好地在早期诊断这些疾病，因为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来测量这种炎症在早期阶段的痴呆症称为轻度认知障碍，或MCI。MCI是不同类型痴呆症的早期阶段，如阿尔茨海默病。我们打算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。PET依赖于特殊设计的放射性化学物质，提供了一种可视化大脑中发生的事情的方法。因此，我们计划开发这种放射性化学物质，用于蛋白质的咪唑啉2结合位点。这种蛋白质存在于一种叫做神经胶质的脑细胞中。这些细胞是大脑的正常部分。然而，在大脑受损和炎症存在的疾病中，有更多的这些细胞，特别是在发炎的区域。我们已经知道，这种蛋白质的数量在死于这些疾病的人的大脑中增加，如阿尔茨海默病。如果我们能在活着的病人身上测量这种蛋白质的变化，这将意味着我们有办法测量这种和类似疾病中发现的大脑炎症，及早给患者最好的治疗机会。

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.