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 [(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 that occurred in vivo. Recently we developed a new ligand, N-acetyl-N-(2-[(11)C]methoxybenzyl)-2-phenoxy-5-pyridinamine [(11)C]PBR28), which showed much greater specific signals than [(11)C]PK11195 in non-human primates. Therefore, [(11)C]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.
Under the current and other protocols using [(11)C]PBR28, we found that some healthy subjects and patients have very low to no binding of [(11)C]PBR28. We scanned approximately 118 subjects in total under protocols using [11C]PBR28 and found that 8% (9/118) had almost no in vivo binding of [(11)C]PBR28. We are also performing in vitro binding assays of [(3)H]PK 11195 or [(3)H]PBR28 with various displacers using lymphocytes. Our preliminary results have shown that some ligands may have similar affinity to PBR28 binders and non-binders. By using [(11)C]PBR28, we need to exclude PBR28 nonbinders from the data to study changes in PBR. By using a PET ligand that binds equally to PBR28 binders and nonbinders, we would be able to study all subjects. We also confirmed that PBR28 nonbinders determined by PET do not show binding in in vitro binding assays using blood cells. Therefore, we wish to test new ligands by obtaining blood samples from additional PBR28 nonbinders and by performing binding assays. Because our preliminary analysis of whole body imaging has shown that the differences between PBR28 binders and nonbinders might somewhat vary among organs, after identifying PBR28 nonbinders by binding assays, we will perform whole body imaging using [(11)C]PBR28.
Purpose
