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 knowledge 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. |