Molecular signaling is a critical therapeutic target in cancer, and molecular therapeutics have achieved some success in treating a variety of cancers. However, our incomplete l^nowledge of pharmacodynamic effects in vivo limits the success of these molecular therapies. We have recently developed a new molecular imaging technique, photothermal optical coherence tomography (OCT), that extends the penetration depth of high resolution molecular Imaging beyond the microscopy limit. The current proposal will further develop photothermal OCT for in vivo imaging of cell receptors, and will combine this new technique with the hemodynamic imaging capabilities of Doppler OCT and spectral microscopy to provide a comprehensive picture of the pharmacodynamic effects of molecular cancer therapies in human cells grown into tumors in the mouse window chamber.
The first aim will use a combined spectral / OCT microscope lo quantify changes in metabolic rate and hemodynamics with tumor growth.
The second aim will develop photothermal OCT for in vivo imaging of cell receptors, and will quantify the pharmocodynamics of receptor inhibition in the mouse window chamber.
The final aim will combine OCT and microscopy to quantify longitudinal changes in receptor expression and hemodyanmic / metabolic response to combination therapies in mouse window chamber tumors. These studies will establish our novel hemodynamic, metabolic and molecular imaging techniques as high resolution, three-dimensional drug screening methods for preclinical applications. This multi-disciplinary environment will provide an excellent opportunity for professional growth and scientific advancement.

Public Health Relevance

This work will develop imaging methods to study the hemodynamic, metabolic and molecular response to drugs in preclinical models, allowing for the formulation of rational dosing and scheduling strategies that iTiaximize the effect of these drugs. In the future, similar technologies coutd be translated to clinical use to provide individualized care to cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
5R00CA142888-04
Application #
8307913
Study Section
Special Emphasis Panel (NSS)
Program Officer
Nordstrom, Robert J
Project Start
2010-09-01
Project End
2013-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$239,534
Indirect Cost
$75,793
Name
Vanderbilt University Medical Center
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Shah, Amy T; Demory Beckler, Michelle; Walsh, Alex J et al. (2014) Optical metabolic imaging of treatment response in human head and neck squamous cell carcinoma. PLoS One 9:e90746
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Tucker-Schwartz, Jason M; Hong, Tu; Colvin, Daniel C et al. (2012) Dual-modality photothermal optical coherence tomography and magnetic-resonance imaging of carbon nanotubes. Opt Lett 37:872-4
Walsh, Alex; Cook, Rebecca S; Rexer, Brent et al. (2012) Optical imaging of metabolism in HER2 overexpressing breast cancer cells. Biomed Opt Express 3:75-85