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Background.Inflammation is involved in many diseases and is commonly denoted with the suffix "-itis" – as in arthritis (inflammation of joints), hepatitis (inflammation of liver), etc. Inflammation is commonly associated with white blood cells (called macrophages) that "eat" the destroyed tissue. In the central nervous system, these cells are called "activated microglia." A quantitative imaging measure of inflammation would help to diagnose disorders and to assess the efficacy of anti-inflammatory treatments.
We developed a few new radioligands that that bind to a protein (PBR) that is associated with macrophages in the periphery and with activated microglia in the brain. These new radioligands appear to have much higher specific signal than an older agent developed several years ago. We tested one of the radioligands in a rat model of stroke, which is surrounded by activated microglia that "eat" the dead cells. The images above show that this radioligand is good enough to image inflammation even in the small rat brain. We subsequently evaluated these ligands in monkeys (see below) and have recently begun imaging of human subjects. By preliminary analysis, the healthy subjects show low binding in brain, consistent with the absence of inflammation. We will soon study patients with neuroinflammation, including multiple sclerosis and AIDS dementia.
Legend. . PET summation image in rhesus brain following injection of [11C]MePPEP. PET images (middle column) were summed from 60 – 120 min. The corresponding MR images are on left column, and the fused PET and MR images are on right column. Upper row: slice including cerebellum and medial and lateral temporal cortex. Middle row: slice including striatum, thalamus, and lateral temporal cortex. Lower row: slice including prefrontal cortex.
References. 1) M. Imaizumi, H.-J. Kim, S.S. Zoghbi, E. Briard, J. Hong, J.L. Musachio, J.M. Hallenbeck, C. Ruetzler, D-M. Chuang, V.W. Pike, R.B. Innis, and M. Fujita. PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat. Neurosci. Lett., 411, 200-205, 2007.
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2) M. Imaizumi, E. Briard, S.S. Zoghbi, J. Hong, J.L. Musachio, R. Gladding, V.W. Pike, R.B. Innis, and M. Fujita. Kinetic evaluation in nonhuman primates of two new PET ligands for peripheral benzodiazepine receptors in brain. Synapse. 61: 595-605, 20, 2007.
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3) M. Fujita, M. Imaizumi, S.S. Zoghbi, Y. Fujimura, A.G. Farris, T. Suhara, J. Hong, V.W. Pike, and R.B. Innis. Kinetic analysis in healthy humans of a novel positron emission tomography radioligand to image the peripheral benzodiazepine receptor, a potential biomarker for inflammation NeuroImage. 40: 43-52, 2008.
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