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500 MHz NMR Spectrometer for Molecular Imaging Applications

$500,000S10FY2007RRNIH

Massachusetts General Hospital, Boston MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Funding is requested for a dedicated 500 MHz high-resolution, solution and magic angle spinning (MAS) Nuclear Magnetic Resonance (NMR) spectrometer. The proposed instrument will be a crucial component in facilitating the development and synthesis of novel molecular imaging contrast agents and for the identification of biomarkers for specific disease states and biological processes. The NMR spectrometer will serve a large NIH-funded geographically diverse user community encompassing a wide variety of biomedical disciplines. We currently serve users both within the MGH/Harvard/MIT system as well as from around the greater Boston/Cambridge region. However, current users do not have sufficient magnet access, and many others would like to take similar advantage of our facilities, but cannot readily do so. Our current wide-bore 600 MHz MR instrument, which is used for liquids, HR-MAS, and CP-MAS NMR spectroscopy as well as MRI, is overscheduled, operating on a 24x7 basis with reservations needing to be made up to 3 months in advance. The long scan times required for obtaining high resolution MR images and the high demand for scan time make it impossible to use the instrument for regular and routine NMR chemical analysis of contrast agents and biological tissues. The requested equipment would greatly expand our capacity to serve the local NIH- funded user community, as well as offer important analytical chemistry capability to the rapidly expanding user base with molecular imaging interests. In particular, the proposed instrument would allow for "walk-on" scan time for the rapid characterization of intermediates in reaction pathways of novel molecular imaging probes currently being developed and for the identification of biomarkers for different disease states. The institutions to be served include MGH (radiology, neurology, pathology, and surgery), Children's Hospital (orthopaedic surgery), Boston University and Northeastern University. Projects requiring solution NMR spectroscopy include the development and synthesis of (1) dual MRI-histology contrast agents for brain molecular imaging, (2) novel blood-brain barrier permeable contrast agents for brain molecular imaging, (3) amyloid plaque targeting contrast agents for Alzheimer's disease studies, (4) targeted drug delivery vehicles, (5) lymph node specific contrast agents, and the identification of biomarkers associated with (6) stroke and (7) Alzheimer's disease. Projects requiring HR-MAS NMR spectroscopy include identifying biomarkers for (1) breast cancer, (2) inflammatory response in burn tissue (3) HIV injured brain tissue, and (4) ostereoporosis. [unreadable] [unreadable] [unreadable]

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