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

神经炎症涉及慢性、缓慢进展的神经变性疾病，例如多发性硬化症、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大脑中称为神经胶质细胞的特定细胞发生的破坏性变化。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。使用非侵入性成像技术拾取损伤的早期迹象或测量脑中胶质细胞的破坏性变化的能力将在神经退行性疾病的临床诊断和管理中具有重要价值。这些活化的小胶质细胞的普遍存在的性质也使得小胶质细胞成为开发治疗或预防许多中枢神经系统疾病的药理学方法的靶标。ANSTO和ANU的研究人员开发了一类新的分子，其靶向一种称为外周苯二氮卓受体或PBR的特定蛋白质，该蛋白质在受损的神经胶质细胞中增强。这些分子的放射性标记的类似物已经证明了在炎症和神经变性的各种动物模型中炎症与该受体的表达之间的强相关性。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伤，并可能减缓疾病的进展。因此，进一步开发这些分子作为非侵入性医学成像的放射性药物和-或作为小胶质细胞激活的抑制剂，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.