In this application for a Mentored Quantitative Research Career Development Award (K25), the candidate's research and career development plans are described. The project is designed to customize the educational and research activities for the candidate to achieve two major goals. The immediate goal is for the candidate to continue his research in amyloid imaging in Alzheimer's disease and aging. The long-term goal is for the candidate to acquire advanced biomedical research skills and develop as an independent researcher in aging-related biomedical imaging. To achieve these goals, the candidate will obtain further trainings in neuroscience, biostatistics, pharmacology, and pharmacokinetics as well as in responsible conduct of biomedical and clinical research. He will also acquire related knowledge through journal clubs, research seminars, lectures, and conferences, and through interaction with other investigators and trainees. The practical skills in biomedical imaging will primarily be obtained through the proposed microPET studies under the guidance of Drs. Mathis and Klunk at the University of Pittsburgh. In this proposed research, the candidate plans to use microPET to evaluate amyloid-imaging agents in transgenic mice models of amyloid deposition. This will allow us for the first time to evaluate the in vivo binding specificity and pharmacokinetic profiles of lead compounds in a CNS model that mimics the future human studies. Therefore, this project will satisfy the following specific aims: 1) rationally design and synthesize a selected array of amyloid-binding agents; 2) evaluate the new compounds for in vitro binding affinity and specificity for amyloid deposits; 3) evaluate selected compounds in ex vivo studies of brain entry, crearance; and metabolism in normal control mice with no amyloid deposits in the brain; 4) use microPET to assess the in vivo properties of selected compounds in amyloid-containing transgenic mouse models to determine in vivo binding specificity and detailed pharmacokinetic profiles. The overall goal of our research is to identify potent, selective, and brain permeable amyloid probes suitable for in vivo human studies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25AG022048-05
Application #
7279281
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Buckholtz, Neil
Project Start
2003-09-30
Project End
2008-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2007
Total Cost
$125,658
Indirect Cost
Name
Case Western Reserve University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Wu, Chunying; Wei, Jingjun; Gao, Kuanqiang et al. (2007) Dibenzothiazoles as novel amyloid-imaging agents. Bioorg Med Chem 15:2789-96
Wu, Chunying; Cai, Lisheng; Wei, Jingjun et al. (2006) Lipophilic analogs of thioflavin S as novel amyloid-imaging agents. Curr Alzheimer Res 3:259-66
Wei, Jingjun; Wu, Chunying; Lankin, David et al. (2005) Development of novel amyloid imaging agents based upon thioflavin S. Curr Alzheimer Res 2:109-14
Wu, Chunying; Pike, Victor W; Wang, Yanming (2005) Amyloid imaging: from benchtop to bedside. Curr Top Dev Biol 70:171-213
Wang, Yanming; Klunk, William E; Debnath, Manik L et al. (2004) Development of a PET/SPECT agent for amyloid imaging in Alzheimer's disease. J Mol Neurosci 24:55-62