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.
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.
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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|
|Walsh, Alex J; Cook, Rebecca S; Sanders, Melinda E et al. (2014) Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Cancer Res 74:5184-94|
|Walsh, Alex J; Cook, Rebecca S; Manning, H Charles et al. (2013) Optical metabolic imaging identifies glycolytic levels, subtypes, and early-treatment response in breast cancer. Cancer Res 73:6164-74|
|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|