Abstract #2789

Measuring the effect of CA-IX inhibition on tumor pH in patient-derived xenografts (PDX) of breast cancer.

William Dominguez-Viqueira¹, Pedro Miguel Enriquez Navas¹, Gary Martinez¹, Epifanio Ruiz ¹, David Morse¹, Robert Gillies¹, and Susan Frost²

¹Department of Cancer Imaging and Metabolism, Moffitt Cancer Center, Tampa, FL, United States, ²Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States

Membrane-bound carbonic anhydrase (CA-IX) plays an important role in maintaining an acidic extracellular pH (pHe) in tumors. We investigate the effect of inhibiting CA-IX on the pHe of patient derived xenografts (PDX) from a triple negative breast cancer using ³¹P MRS of 3-aminopropylphosphonate (3-APP) as a pH biomarker. Mice were imaged before the injection of the ureido-sulfonamide CA-IX inhibitor (cpd25) and again at 2.5 and 24 hours after injection. There was an increase in pH in 5/6 animals in the first 24 hours. This is first in vivo evidence that CA-IX inhibition disrupts pH in vivo.

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