Multimodality pH imaging in a mouse dorsal skin fold window chamber model.
Upregulate levels of expression and activity of membrane H+ion pumps in cancer cells drives the extracellular pH (pHe,) 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 pHecould be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHein 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 pHe, 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 pHeof 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 pHethe chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHein 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 pHe.
University of Arizona, College of Optical Sciences; University of Arizona, Department of Medical Imaging.
Hui Min
HM
Leung
University of Arizona, Biomedical Engineering.
Rachel
R
Schafer
University of Arizona, Department of Medical Imaging; University of Arizona, Biomedical Engineering; University of Arizona, Arizona Cancer Center.
Mark M
MM
Pagel
University of Arizona, Arizona Cancer Center.
Ian F
IF
Robey
University of Arizona, College of Optical Sciences; University of Arizona, Department of Medical Imaging; University of Arizona, Biomedical Engineering.
Arthur F
AF
Gmitro
CEST; MRI; acidosis; cancer; confocal; fluorescence; in vivo imaging; microenvironment; pH; window chamber
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