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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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