title: In Vivo Imaging of Tumor Metabolism and Acidosis by Combining PET and MRI-CEST pH Imaging.
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 tumor18F-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 of18F-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 and18F-FDG uptake, as a high18F-FDG uptake corresponds to lower extracellular pH values. These results show how merging the information from18F-FDG-uptake and extracellular pH measurements can improve characterization of the tumor microenvironment. Cancer Res; 76(22); 6463-70. ©2016 AACR.
authors.affiliation: Institute of Biostructure and Bioimaging (CNR) c/o Molecular Biotechnologies Center, Torino, Italy.|Molecular Imaging Center, University of Torino, Torino, Italy.
authors.forename: Dario L
authors.initials: DL
authors.lastname: Longo
authors.affiliation: Molecular Imaging Center, University of Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bartoli
authors.affiliation: Molecular Imaging Center, University of Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Consolino
authors.affiliation: Molecular Imaging Center, University of Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bardini
authors.affiliation: Molecular Imaging Center, University of Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Arena
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Molecular Imaging Center, University of Torino, Torino, Italy. silvio.aime@unito.it.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000138:Acidosis; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*