Magnetic resonance imaging is more sensitive than PET for detecting treatment-induced cell death-dependent changes in glycolysis
Author(s)
Type
Journal Article
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.
Date Issued
2019-07-15
Date Acceptance
2019-05-10
Citation
Cancer Research, 2019, 79 (14), pp.3557-3569
ISSN
0008-5472
Publisher
American Association for Cancer Research
Start Page
3557
End Page
3569
Journal / Book Title
Cancer Research
Volume
79
Issue
14
Copyright Statement
Copyright © This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31088837
PII: 0008-5472.CAN-19-0182
Subjects
CRITERIA
EXPRESSION
FLUORODEOXYGLUCOSE
LACTATE
Life Sciences & Biomedicine
MACROPHAGES
METABOLISM
MOUSE
Oncology
Science & Technology
THERAPY
TUMOR RESPONSE
VALIDATION
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-07-15