Primary Outcome Measures:
- Biodistribution of [C-11]PBR28
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 [11C]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 that occurred in vivo. Recently we developed a new ligand, N-acetyl-N-(2-[11C]methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28), which showed much greater specific signals than [11C]PK11195 in non-human primates. Therefore, [11C]PBR28 is a promising PET ligand. However, radiation absorbed doses have not been estimated from human whole body imaging.
The initial purpose of this protocol is to estimate radiation absorbed doses of [11C]PBR28 by performing whole body imaging studies on ten healthy human subjects. The results of this overall study are required to apply this PET ligand in various neurological and psychiatric disorders in the future. The secondary purpose is to compare in vivo and in vitro binding of PBR28 by performing whole body PET scans and in vitro binding assays using blood cells for the following reasons. Under the current and other protocols using PBR28, we found that approximately 15 percent (3/20) of subjects did not have in vivo binding of PBR28. We also performed an in vitro binding assay of PBR28 using lymphocytes of one of the in vivo non-binders and found the presence of specific binding in vitro. We plan to find a percentage of non-binders and study if there is really discrepancies between in vivo and in vitro binding.
Purpose
