3 March 2022Measurement of intact and dissociated porphyrin-lipid nanoparticle concentration in tissue using diffuse reflectance and fluorescence spectroscopy
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We present ongoing work to develop and verify a measurement technology using diffuse reflectance spectroscopy and fluorescence spectroscopy to measure in-vivo concentrations of intact and dissociated porphysomes. Porphysomes (PS) are multifunctional liposome-like nanoparticles composed of porphyrin-lipid subunits that exhibit structure-dependent optical quenching. They are attractive as agents for photothermal and photodynamic therapy but methods are required for measuring their concentration in the intact and dissociated states for treatment dosimetry and guidance. Diffuse reflectance spectroscopy is used here to measure concentrations of intact and dissociated (unquenched) PS using their unique absorption spectra, and also to correct the fluorescence signal for the optical properties of the tissue. The latter is then used to quantify the fluorescence (QF) signal from dissociated PS, providing a more direct measure of photodynamic activity. Two experiments were performed for proof-of-concept. First, a liquid phantom was used to verify measurements taken with a combined reflectance-fluorescence probe. This demonstrated that the reflectance signal was sensitive to the relative proportion of intact and dissociated PS and that the QF signal contained information about the PS unquenching. Second, a mouse model was used to demonstrate that the drop in the reflectance signal at the PS absorption peak wavelength and the fluorescence signal are consistent with Positron Emission Tomography (PET) measurements of copper-64 labeled PS.
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Theo Husby, Michael Valic, Gang Zheng, Brian C. Wilson, Robert Weersink, "Measurement of intact and dissociated porphyrin-lipid nanoparticle concentration in tissue using diffuse reflectance and fluorescence spectroscopy," Proc. SPIE 11938, Visualizing and Quantifying Drug Distribution in Tissue VI, 1193806 (3 March 2022); https://doi.org/10.1117/12.2609870