In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging

  • Authors:
    • Annasofia Anemone
    • Lorena Consolino
    • Laura Conti
    • Francesca Reineri
    • Federica Cavallo
    • Silvio Aime
    • Dario Livio Longo
  • View Affiliations

  • Published online on: June 7, 2017     https://doi.org/10.3892/ijo.2017.4029
  • Pages:498-506
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Abstract

Dichloroacetate (DCA) can reverse the glycolytic phenotype that is responsible of increased lactate production and extracellular pH acidification in cancer cells. Magnetic resonance imaging-chemical exchange saturation transfer (MRI-CEST) pH mapping is a novel non-invasive imaging approach that can measure in vivo extracellular tumour pH. We examined whether MRI-CEST pH mapping can monitor in vivo changes in tumour acidosis for assessing treatment response to DCA. Cell viability and extracellular pH were assessed in TS/A breast cancer cells treated with 1-10 mM DCA for 24 h in normoxia or hypoxia (1% O2) conditions. Extracellular tumour pH values were measured in vivo by MRI-CEST pH mapping of TS/A tumour-bearing mice before, three days and fifteen days after DCA or saline treatment. Reduced extracellular acidification and vitality were observed in DCA-treated TS/A cells. Tumour-bearing mice showed a marked and significant increase of tumour extracellular pH at 3 days post-DCA treatment, reflecting DCA-induced glycolysis inhibition, as confirmed by reduced lactate production. After 15 days of DCA treatment, the onset of resistance to DCA was observed, with recover of tumour extracellular acidification and lactate levels that returned to baseline values. A significant correlation was observed between tumour extracellular pH values and lactate levels (r= -0.97, P<0.05). These results suggest that MRI-CEST pH imaging is a promising tool to monitor the early response and efficacy of cancer metabolic targeting drugs.

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August 2017
Volume 51 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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APA
Anemone, A., Consolino, L., Conti, L., Reineri, F., Cavallo, F., Aime, S., & Longo, D.L. (2017). In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging. International Journal of Oncology, 51, 498-506. https://doi.org/10.3892/ijo.2017.4029
MLA
Anemone, A., Consolino, L., Conti, L., Reineri, F., Cavallo, F., Aime, S., Longo, D. L."In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging". International Journal of Oncology 51.2 (2017): 498-506.
Chicago
Anemone, A., Consolino, L., Conti, L., Reineri, F., Cavallo, F., Aime, S., Longo, D. L."In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging". International Journal of Oncology 51, no. 2 (2017): 498-506. https://doi.org/10.3892/ijo.2017.4029