In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging
In vivo evaluation of tumour acidosis for assessing the early metabolic response and onset of resistance to dichloroacetate by using magnetic resonance pH imaging(68 visite) Anemone A, Consolino L, Conti L, Reineri F, Cavallo F, Aime S, Longo DL
Int J Oncol (ISSN: 1019-6439, 1791-2423electronic), 2017 Aug; 51(2): 498-506.
Tipo di articolo: Journal Article,
Impact factor: 3.333, Impact factor a 5 anni: 3.271
*** IBB - CNR *** Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy., National Research Council of Italy (CNR), Institute of Biostructure and Bioimaging, Molecular Imaging Center, 10126 Turin, Italy.,
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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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501 Records (425 escludendo Abstract e Conferenze). Impact factor totale: 1698.347 (1461.073 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 1777.293 (1526.807 escludendo Abstract e Conferenze).
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