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2007 Scientific Report

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VARI | 2007 A new radiation biology project this year, in collaboration with Weiwen Deng and Aly Mageed of DeVos Children’s Hospital, investigates a new approach for treating graft-versus-host disease in mice undergoing bone marrow transplantation, with planned extension to human patients in the near future. Our major established project in nuclear medicine continues work initiated by Dr. Hay and colleagues while he was a member of the Laboratory of Molecular Oncology. Since 2001 we have been evaluating radioactive antibodies and smaller molecules that attach to the Met receptor tyrosine kinase, collectively designated Met-avid radiopharmaceuticals (MARPs). Met plays a key role in causing cancers to become more aggressive, so that they spread to nearby tissues (invasion) and/or travel through the bloodstream or lymph channels to distant organs (metastasis). We previously showed that both large and small MARPs are useful for nuclear imaging of Met-expressing human tumors (xenografts) grown under the skin of immunodeficient mice. During the past year, in collaboration with our colleagues at VARI and with our outside collaborators at DVAHS, ApoLife, and MSU, we have been evaluating new ways of complexing radioactive atoms with MARPs for improved ease of use and future clinical applications. In 2006 we began a multimodality noninvasive imaging program for evaluating the growth, Met expression, and response to therapy of aggressive human tumor xenografts grown orthotopically in immunodeficient mice. Employing a combination of high-resolution ultrasound with and without contrast agents, planar and tomographic nuclear imaging, and CT imaging, we are now acquiring data for tumors of the brain, pancreas, adrenals, and bone. External Collaborators 33 Our lab depends critically on intramural and extramural collaborations to address our research themes. Our extramural collaborators include scientists and physicians at the Department of Veterans Affairs Healthcare System in Ann Arbor; the University of Michigan in Ann Arbor; Michigan State University in East Lansing; ApoLife, Inc., in Detroit; Henry Ford Hospital in Detroit; West Michigan Heart, P.C., in Grand Rapids; DeVos Children’s Hospital in Grand Rapids; St. Mary’s Health Care in Grand Rapids; Fred Hutchinson Cancer Research Center in Seattle; the Gerald P. Murphy Foundation in West Lafayette, Indiana; the National Cancer Institute in Bethesda, Maryland; the University of Illinois in Champaign-Urbana; and VisualSonics, Inc., in Toronto. Recent Publications Meng, L.J., N.H. Clinthorne, S. Skinner, R.V. Hay, and M. Gross. 2006. Design and feasibility study of a single photon emission microscope system for small animal I-125 imaging. IEEE Transactions on Nuclear Science 53(3): 1168–1178. Hay, R.V., and M.D. Gross. 2006. Scintigraphic imaging of the adrenals and neuroectodermal tumors. In Nuclear Medicine, 2nd edition, R.E. Henkin, D. Bova, G.L. Dillehay, S.M. Keresh, J.R. Halama, R.H. Wagner, and A.M. Zimmer, eds. Philadelphia: Mosby Elsevier, pp. 820–844.

Van Andel Research Institute | Scientific Report Office of Translational Programs Since July 2005 the Office of Translational Programs (OTP) has been the administrative home base for activities overseen by the Deputy Director for Clinical Programs. The role of OTP is to promote and facilitate collaborative programs involving the Van Andel Research Institute and other institutions in the realm of translational medicine. OTP accomplishments during our second year of formal operation include the following. • Serving as the administrative home for the GMP facility. With funding from the state of Michigan and the federal Health Resources and Services Administration, VARI and Grand Valley State University have partnered to build and operate Grand River Aseptic Pharmaceutical Packaging (GR-APP), a Good Manufacturing Practices facility that will package pharmaceuticals for early-phase clinical trials commissioned by academic and commercial investigators, primarily in Michigan and the Midwest. As of this writing, construction of GR-APP is nearing completion, and we expect operations to begin by autumn of 2007. • Serving as the administrative home for the West Michigan Chapter of the Michigan Cancer Consortium (MCC). As an active member of the MCC, VARI is committed to participating in statewide programs to reduce the burden of cancer in Michigan. In 2005, we and other regional MCC members launched an initiative to develop community-based programs more relevant to western Michigan. Our first project, designated “C-Works!”, will provide cancer screening and follow-up services to uninsured working women in Kent County. 34 • Organizing and hosting meetings. In October 2006, OTP hosted the Great Lakes Regional Meeting of the American Cancer Society at VARI (Troy Giambernardi, Conference Chair) and assisted with preparations for the fall meeting of the Central Chapter-Society of Nuclear Medicine in Traverse City (Rick Hay, Conference Co-Chair). In November 2006, OTP assisted with local arrangements for the annual meeting of the Michigan Cancer Consortium at DeVos Hall. • Promoting new interinstitutional collaborations and providing resources for funding proposals. OTP provides a broad range of administrative assistance, logistical support, grant preparation expertise, meeting venues, and seed funding for new interinstitutional collaborations seeking extramural funding from state, federal, or private sources. During this past year we helped secure state funding for ClinXus, a west Michigan–based consortium for conducting innovative clinical trials, and we are awaiting the outcomes of recent collaborative proposals submitted to NIH and to two private foundations. • Coordinating research rotations for physicians-in-training. In collaboration with the Grand Rapids Medical Education and Research Consortium (MERC), we schedule each first-year general surgery resident to spend one month working in a designated research laboratory at VARI. This program has been well received by both residents and VARI investigators. Custom-tailored rotations of variable duration at VARI can be arranged for other physicians-in-training. Staff Rick Hay, Ph.D., M.D., F.A.H.A. Troy Carrigan Jean Chastain

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