Near-infrared fluorescence (NIRF)-based optical imaging of human cancers has several advantages over standard imaging techniques in that it is extremely sensitive, inexpensive, and robust;involves no harmful radiation;and allows real-time visualization. The development of well-validated NIRF imaging probes may lead to this new modality becoming clinically viable for molecular imaging. Recent advances in nanotechnology are likely to substantially accelerate the discovery of new NIRF imaging agents that can not only provide increased signal intensity, but also target or """"""""report"""""""" both the presence and the biologic activity of tumor-specific biomarkers. In this application, U. T. M. D Anderson Cancer Center, a leading institution in cancer research and patient care, and Eastman Kodak Co., a world leader in the fabrication of optical dyes and nanoparticles, will team to develop novel nanoparticles for molecular optical imaging applications. Our goals are to systematically investigate the in vivo pharmacologic properties of nanoparticles derived from Kodak's platform technology, and to design and develop nanoparticles that use targeting, enzyme activation, or a combination of both features to achieve significant improvements in the sensitivity and specificity of cancer detection.
Our specific aims are 1) to synthesize and characterize polymer-shelled silica nanoparticles and cross-linked PEG nanoparticles suitable for NIRF imaging;2) to establish the effect of particle characteristics on the pharmacokinetics, biodistribution, clearance, extravasation, and intratumoral distribution of NIRF nanoparticles;3) to establish the stability and signal intensity of NIRF nanoparticles in vivo and the specificity of their retention in tumors;4) to construct NIRF nanoparticles targeted to angiogenic blood vessels and to tumor cell-associated surface receptors;and 5) to develop smart, activatable NIRF nanoparticles and to combine homing ligand and molecular beacon designs in a single nanoparticulate system. By using a combination of nuclear and optical imaging, autoradiography, and fluorescence microscopy, we expect to provide detailed insights into the pharmacologic properties of NIRF nanoparticles, with the ultimate goal of obtaining nanoparticles that are effective and practical for molecular optical imaging of human cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA119387-05S1
Application #
7919135
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (O1))
Program Officer
Grodzinski, Piotr
Project Start
2009-09-29
Project End
2011-09-29
Budget Start
2009-09-29
Budget End
2011-09-29
Support Year
5
Fiscal Year
2009
Total Cost
$320,000
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Radiation-Diagnostic/Oncology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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