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Abstract

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.  

Author information​

Longo DL1,2, Bartoli A2,3, Consolino L2,3, Bardini P2,3, Arena F2,3, Schwaiger M4, Aime S5,3.

1Institute of Biostructure and Bioimaging (CNR) c/o Molecular Biotechnologies Center, Torino, Italy.

2Molecular Imaging Center, University of Torino, Torino, Italy.

3Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

4Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany.

5Molecular Imaging Center, University of Torino, Torino, Italy. silvio.aime@unito.it.