This laboratory has made progress in two general areas: programmatic and specific radioligands.? PROGRAMMATIC.? 1) The Biomarkers Consortium approved the proposal of Victor Pike and me to develop further a PET radioligand for inflammation. The Biomarkers Consortium is a collaboration of NIH, FDA, and the pharmaceutical industry and is managed by the Foundation for NIH. The radioligand labels phagocytic inflammatory cells: macrophages in periphery and activated microglia in the brain. We are now planning specific studies to evaluate and disseminate this radioligand for use in multiple PET Centers.? 2) Dr. Pike (Director of Radiochemistry) and I post our radioligand information on a public web site to assist the PET community. More specifically, we post the IND (Investigation New Drug) application, including toxicology information and detailed chemical synthesis, the FDA review, and our response to review.? 3) I directed an international group of experts to propose a consensus nomenclature for PET imaging, and the resulting paper was recently published. The PET community uses many different terms and abbreviations. This consensus will help clarify terms for the research community.? 4) Dr. Pike and I continue to direct a joint PhD program in neuroscience with NIH and the Karolinska Institutet (Stockholm, Sweden). We now have about 25 graduate students, about half Swedish and half American. Students have two mentors (one from each institution), spend about half time at each institution. The program has been quite successful, and our first class of students is now receiving PhD degrees.? 5) I wish the NIMH PET program to be a national resource to extramural sites. Towards this goal, I established useful collaborations with two nearby institutions in which patients receive state-of-the-art PET scans at NIMH. For example, we are studying a novel radioligand for amyloid in patients with Alzheimer's disease, recruited and studied by Paul Aisen (Georgetown). In addition, Justin McArthur (Johns Hopkins) will soon send patients with neurAIDS to NIMH to be scanned with a novel radioligand for inflammation. If the results are successful, the collaborating institution can use the data as preliminary results in a grant application.? ? ? SPECIFIC RADIOLIGANDS. During the prior year (October 2006 - September 2007), our projects have included:? 1) Development of a probe for Alzheimer's disease. Significant progress has been made to develop a probe that could be used to diagnose and monitor Alzheimer's disease by labeling a protein that accumulates in the brains of patients with this disorder.? ? 2) Evaluation of a probe for intracellular signals. Most of the available probes label targets (or receptors) located on the outside of the cell. We are now examining a probe for an intracellular target (phosphodiesterase) that is believed to be involved in the therapeutic actions of antidepressant treatments.? ? 3) Probe for the cannabinoid receptor, which mediates the effects of marijuana.? ? 4) Probe to measure inflammatory cells. ? ? 5) Probe to measure a transporter pump at the blood-brain barrier.
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