Changes in cellular metabolism, perfusion, and proton export that occur during indolent-to-aggressive transition in prostate cancer (PCa) likely lead to a lower extracellular pH (pHe) in vivo, promoting an aggressive, treatment-resistant phenotype. To measure this interstitial acidification, we implemented a hyperpolarized (HP) imaging protocol that measured lactate-to-pyruvate ratio, perfusion, and pHe in a murine model of prostate cancer, the TRAMP mouse. Our results indicated higher pyruvate-to-lactate conversion, lower perfusion, and lower pHe in high-grade tumors, suggesting a correlation between the three parameters and implicating low pHe in the development of aggressive PCa.
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