Thursday, April 30, 2009

Monitoring Response to Thermodox using Optical Spectroscopy

Greg Palmer Ph.D. present his post-doc work in Dr. Dewhirst's Lab:

Optical spectoscopy involves measuring the reflectance, and fluorescence of tissue, and looking to provide structural and functional information. This is a non-invasive, near real-time, non-destructive measurement.

Three properties are measured: absorbance, scattering, and fluorescence.

Measurable Quantities:
Hb concentrations and saturation
Amino Acids
Extrinsic Fluorecence (doxorubicin and other drugs or contrast agents)
Size and density of scattering centers (collagen structure)

Depth may be done up to 5cm when utilizing infrared wavelengths (though with shorter wavelengths, we may be limited to millimeters).

Measurement within 10% can be arrived at via monte carlo model fit for hemoglobin concentrations. PO2 can thereby also be estimated. This contrasts to BOLD imaging which only measures relative change.

Note that the measurements are volume averaged, thus less sensitive to positition than an ependorf electrode.

Thermodox is doxorubicin encapsulated within a thermally sensitive liposome. This is given in combination with regional hyperthermia for directed chemotherapy delivery. As doxorubicin is fluorescent (593nm), measurements with optical spectroscopy can estimate in real time, regional drug concentrations may be estimated.

Concentrations as estimated by optical spectroscopy and correlated to HPLC assay as reference resulted in excellent correlation r=0.9, p=1e-20.

Hb saturation and concetration both are seen to increase after hyperthermia. In the setting of liposomal doxorubin, these do not increase, which may be a result of doxorubicin's direct affect on vasculature. One can see a dramatic increase in doxorubicin after application of hyperthermia to liposomal doxorubicin, much greater than free dox +HT, or free dox alone.

Ongoing clinical work is progressing in Head and Neck, Breast, and Cervical Cancer... stay tuned.

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