Bicarbonate-free pH neutralization resensitizes ovarian cancer to chemotherapy and is tracked by 3T CEST MRI

In OVCAR3 and SKOV-3 ovarian cancer models, inhibiting MCT4 with acriflavine reverses acidosis-linked chemoresistance, with baseline and normalization tracked by 3T acidoCEST MRI.

• Why it matters: Tumor acidosis is linked to relapse after platinum-taxane chemotherapy, yet bicarbonate-based neutralization has not translated clinically.
• What they did: Cells overexpressed MCT1 and MCT4 under acidosis; acriflavine reduced extracellular acidification at noncytotoxic doses and reversed acidosis-driven increases in paclitaxel and carboplatin IC50 values. In SKOV-3 tumors, acidoCEST MRI with iopromide measured baseline acidosis and its normalization after acriflavine.
• The result: Tumor acidosis is imageable and druggable, and bicarbonate-free pH neutralization can resensitize ovarian cancer to frontline chemotherapy in these preclinical systems.

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