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Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis.

Accepted version
Peer-reviewed

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Authors

Hesketh, Richard L 
Wang, Jiazheng 

Abstract

Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented <5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake. SIGNIFICANCE: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death.

Description

Keywords

Adenocarcinoma, Animals, Antineoplastic Agents, Carbon Isotopes, Cell Death, Cell Line, Tumor, Colorectal Neoplasms, Female, Fluorodeoxyglucose F18, Glycolysis, Heterografts, Humans, Lactic Acid, Magnetic Resonance Imaging, Mice, Inbred BALB C, Mice, Nude, Positron-Emission Tomography, Pyruvic Acid, Radiopharmaceuticals, Receptors, TNF-Related Apoptosis-Inducing Ligand, Triple Negative Breast Neoplasms

Journal Title

Cancer Res

Conference Name

Journal ISSN

0008-5472
1538-7445

Volume Title

79

Publisher

American Association for Cancer Research (AACR)

Rights

All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (C14303/A17197)
Aarhus University (Source: Data Science Research Centre (DSRC)) (15952)
Cancer Research UK (25040)
Rosetrees Trust (A1698)
Rosetrees Trust (M723)
Cancer Research UK (17242)