Multimodality pH imaging in a mouse dorsal skin fold window chamber model

Hui Min Leung; Rachel Schafer; Mark M. Pagel; Ian F. Robey; Arthur F. Gmitro

doi:10.1117/12.2005472

13 March 2013 Multimodality pH imaging in a mouse dorsal skin fold window chamber model

Hui Min Leung, Rachel Schafer, Mark M. Pagel, Ian F. Robey, Arthur F. Gmitro

Proceedings Volume 8574, Multimodal Biomedical Imaging VIII; 85740L (2013) https://doi.org/10.1117/12.2005472
Event: SPIE BiOS, 2013, San Francisco, California, United States

Abstract

Upregulate levels of expression and activity of membrane H⁺ ion pumps in cancer cells drives the extracellular pH (pH_e,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pH_e could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pH_e in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pH_e, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pH_e of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pH_e the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pH_e.

Citation Download Citation

Hui Min Leung, Rachel Schafer, Mark M. Pagel, Ian F. Robey, and Arthur F. Gmitro "Multimodality pH imaging in a mouse dorsal skin fold window chamber model", Proc. SPIE 8574, Multimodal Biomedical Imaging VIII, 85740L (13 March 2013); https://doi.org/10.1117/12.2005472

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