Keywords: Other Preclinical, Molecular Imaging, Prostate Cancer Models, Lonidamine, mito-Lonidamine, 1H and 31P MRS, Seahorse, oxygen consumption rate, pH
Motivation: When prostate cancer is treated with external beam radiation therapy (RT) with doses up to 78 Gy, gastrointestinal and genitourinary toxicities are often observed.
Goal(s): Tumor sensitization by mito-lonidamine (mito-LND) will lower RT doses reducing the risk of adverse effects.
Approach: The effects were assessed in vitro and in vivo in prostate cancer models using Seahorse, 1H and 31P MRS respectively.
Results: Our findings showed a sustained and tumor-selective decrease in intracellular pH, bioenergetics, oxygen consumption rate and lactate. Selective tumor acidification, deenergization and oxygenation induced by mito-LND may improve the radiation response in prostate cancer.
Impact: Exploiting the modulation of tumor metabolism and microenvironment for improving therapeutic efficacy of radiation therapy (RT) in early stage prostate cancer will lead to improved outcomes in prostate cancer patients.
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