Novel radiolabelled peripheral benzodiazepine receptor (PBR) ligands for imaging and treating neuroinflammation

神经炎症与慢性、缓慢进展的神经退行性疾病有关，如多发性硬化症、阿尔茨海默病、帕金森病和亨廷顿病。在神经炎症的发展和这些疾病的进展中，一个重要的早期特征是发生在大脑中被称为神经胶质细胞的特定细胞上的破坏性变化。这些变化被称为小胶质细胞激活，导致大脑区域屈服于进行性疾病和组织破坏。利用无创成像技术获取损伤的早期迹象或测量大脑神经胶质细胞的破坏性变化的能力在神经退行性疾病的临床诊断和治疗中具有重要价值。这些被激活的小胶质细胞的普遍特性也使得小胶质细胞成为治疗或预防许多中枢神经系统疾病的药理学方法发展的目标。ANSTO和ANU的研究人员已经开发出一种新型分子，其目标是一种被称为外周苯二氮卓受体（peripheral benzodiazepine receptor，简称PBR）的特定蛋白质，这种蛋白质在受损的神经胶质细胞中会增强。这些分子的放射性标记类似物已经在各种炎症和神经变性动物模型中证明了炎症和该受体表达之间的强烈相关性。此外，这些分子有可能抑制对这些神经胶质细胞的进一步损害，并有可能减缓疾病的进展。因此，进一步开发这些分子，无论是作为无创医学成像的放射性药物，还是作为小胶质细胞激活的抑制剂，都可能对神经退行性疾病的理解、管理和治疗产生重大影响。

Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destruction. The ability to pickup early signs of injury or to measure destructive changes to glial cells in the brain using noninvasive imaging techniques would be of great value in the clinical diagnosis and management of neurodegenerative disease. The ubiquitous nature of these activated microglia also makes the microglia a target for the development of pharmacological approaches to the treatment or prevention of many central nervous system diseases. Researchers at ANSTO and the ANU have developed a novel class of molecules, which target a specific protein called the peripheral benzodiazepine receptor or PBR which is enhanced in damaged glia. Radiolabelled analogues of these molecules have demonstrated a strong correlation between inflammation and the expression of this receptor in various animal models of inflammation and neurodegeneration. Furthermore, these molecules have the potential to inhibit further damage to these glial cells and could potentially slow down the progression of the disease. Therefore, further development of these molecules both as radiopharmaceuticals for noninvasive medical imaging and-or as inhibitors of microglial activation could have a significant impact on the understanding, management and treatment of neurodegenerative disease.