The era of molecular imaging necessitates the development of molecular probes that can interrogate the molecular basis of pathogenesis. Unfortunately, aberrant molecular processes in vivo typically involve the expression of small amounts of target factors that can only be detected by highly sensitive diagnostic methods. For this reason, nuclear imaging methods, which can detect minimal amounts of radiopharmaceuticals in tissues, are suited for molecular imaging. Recent studies have shown that accurate and rapid detection of cancer cells can be achieved by the use of multimodal imaging systems to furnish complementary and unique diagnostic information from each component imaging method. Molecular imaging of cancer in vivo by multimodality imaging methods would benefit from the development of monomolecular multimodality imaging agents (MOMIAs). Accordingly, this study focuses on the development of novel optical-nuclear MOMIAs for imaging tumors. The structural framework of the proposed molecules will consist of a receptor-specific carrier to enhance tumor specificity, a NIR fluorescent dye for optical imaging, and a chelated radiometal for gamma scintigraphy (111In), positron emission tomography (64Cu) or combined gamma scintigraphy and radiotherapy (177Lu). Stability, cytotoxicity and subcellular distribution of the new MOMIAs will be performed to select promising candidates for in vivo evaluation. The in vivo studies will include pharmacokinetics and histology of selected MOMIAs. Localization of tumors in rodents will be performed by fluorescence, gamma, and positron emission imaging, and the data from all modalities will be compared with each other. Successful completion of this study will result in the development of at least one MOMIA for translational research and eventual clinical use.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA100972-04
Application #
7060838
Study Section
Special Emphasis Panel (ZCA1-SRRB-9 (J2))
Program Officer
Menkens, Anne E
Project Start
2003-05-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2008-04-30
Support Year
4
Fiscal Year
2006
Total Cost
$455,692
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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