At the University Hospital Vrije Universiteit the PET ligand PK11195 labeled with carbon-11, (R)-[11C]PK11195, will be used to study microglia activation in-vivo in patients with traumatic brain damage, Alzheimer disease, multiple sclerosis and neuritis optica, disorders with unknown pathophysiology and treatment difficulties.~PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3 isoquinolinecarboxamide) is a highly specific ligand for the peripheral benzodiazepine-binding site, which is particularly abundant on cells of the mononuclear macrophage line (Myers et al., 1991). In normal human brain, the peripheral-type benzodiazepine receptor ligand PK11195 exhibits low to minimal binding primarily associated with the choroid plexus, ependymal linings and glial cells. However, following neuronal damage, the cells involved in the ensuing gliosis, microglia, show a marked increase in expression of these sites (Stephenson et al., 1995;Conway et al., 1998).~PK11195 labeled with carbon-11 is a PET ligand to peripheral type benzodiazepine receptors which has already been used in patients with stroke (Ramsay et al., 1992), Rasmussen's encephalitis (Banati et al., 1999), multiple sclerosis (Banati et al., 1997) and facial nerve lesions (Myers et al., 1999). However, no tracer kinetic model for quantification has been fully validated for(R)-[11C]PK11195. In order to use (R)-[11C]PK11195 for PET-imaging of microglia activation and to use it in the longitudinal monitoring of disease progression, baseline levels of ligand uptake in a healthy control population are required. This study aims to measure (R)-[11C]PK11195 uptake in normal brain in different age groups and to develop methods for quantification of specific binding of (R)-[11C]PK11195. Because (R)-[11C]PK11195 uptake depends on regional bloodflow, each (R)-[11C]PK11195 scan will be preceded by a cerebral bloodflow scan with H215O.~OBJECTIVES~Determine the distribution of (R)-[11C]PK11195 in normal brain~Develop methods for quantification of specific binding of (R)-[11C]PK11195~Determine the metabolic profile of (R)-[11C]PK11195 in healthy volunteers~DESIGN OF THE STUDY Forty healthy subjects will be recruited, 20 males and 20 females. This is an open study. The study consists of one PET scan, which will be performed at the Department of Nuclear Medicine & PET research of the VU University Medical Centre.
This is a study using Positron Emission Tomography (PET) to study the normal distribution of the PET ligand (R)-[11C]PK11195. This ligand will be used to study inflammation in the brain in several brain disorders like Alzheimer's disease and traumatic brain injury.