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

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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.