PET Imaging of Brain Peripheral Benzodiazepine Receptors

The peripheral benzodiazepine receptor (PBR) is distinct from central benzodiazepine receptors associated with GABA(A) receptors. Although PBR was initially identified in peripheral organs such as kidneys, endocrine glands and lungs, later studies identified PBR in the central nervous system. In normal conditions, PBR is expressed in low levels in some neurons and glial cells. PBR can be a clinically useful marker to detect neuroinflammation because activated microglial cells in inflammatory areas express much greater levels of PBR than in microglial cells in resting conditions. PBR has been imaged with positron emission tomography (PET) using \[(11)C\]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195). However, this classical ligand provides only low levels of specific signals and is not sensitive to detect changes occurred in vivo. Recently we developed a new ligand, N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine \[(11)C\]PBR28, which showed much greater specific signals than \[(11)C\]PK11195 in non-human primates. In the present protocol, we plan to perform a kinetic brain imaging study in healthy human subjects to measure PBR in brain regions with \[(11)C\]PBR28. Successful development of a PET ligand to image PBR will have a strong impact on clinical management of brain disorders with inflammation such as multiple sclerosis and ischemia and neurodegenerative disorders such as Alzheimer's and Parkinson's disease where inflammation is involved in the disease progression.