The vast majority of
cancers exhibit increased
glucose uptake and glycolysis regardless of
oxygen availability. This metabolic shift leads to an enhanced production of
lactic acid that decreases extracellular pH (pHe), a hallmark of the tumor microenvironment. In this way, dysregulated
tumor pHe and upregulated
glucose metabolism are linked tightly and their relative assessment may be useful to gain understanding of the underlying biology. Here we investigated noninvasively the in vivo correlation between
tumor 18F-FDG uptake and extracellular pH values in a murine model of HER2+
breast cancer.
Tumor extracellular pH and perfusion were assessed by acquiring MRI-CEST (chemical exchange saturation transfer) images on a 3T scanner after
intravenous administration of a pH-responsive
contrast agent (
iopamidol). Static PET images were recorded immediately after MRI acquisitions to quantify the extent of
18F-FDG uptake. We demonstrated the occurrence of
tumor pHe changes that report on acidification of the interstitial fluid caused by an accelerated glycolysis. Combined PET and MRI-CEST images reported complementary spatial information of the altered
glucose metabolism. Notably, a significant inverse correlation was found between extracellular
tumor pH and
18F-FDG uptake, as a high
18F-FDG uptake corresponds to lower extracellular pH values. These results show how merging the information from 18F-FDG-uptake and extracellular pH measurements can improve characterization of the tumor microenvironment.
Cancer Res; 76(22); 6463-70. ©2016 AACR.