Journal article
Hyperpolarized C-13 Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential
Metabolites, Vol.11(5), 274
05/01/2021
DOI: 10.3390/metabo11050274
PMCID: PMC8145849
PMID: 33925445
Abstract
This study uses dynamic hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, n = 7) and metastatically dormant (4T07, n = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (k(PL)) and lactate-to-pyruvate area-under-the-curve ratio (AUC(L/P)) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing k(PL) (p = 0.17) and AUC(L/P) (p = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-alpha (HIF-1 alpha), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUC(L/P) was significantly correlated with tumor LDH activity (rho(spearman) = 0.621, p = 0.027) and blood glucose levels (rho(spearman) = -0.474, p = 0.042). k(PL) displayed a similar, non-significant trend for LDH activity (rho(spearman) = 0.480, p = 0.114) and blood glucose levels (rho(spearman) = -0.414, p = 0.088). Neither k(PL) nor AUC(L/P) were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUC(L/P) and tumor LDH activity indicates the potential of AUC(L/P) as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.
Details
- Title: Subtitle
- Hyperpolarized C-13 Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential
- Creators
- Erin B. Macdonald - University of Wisconsin–MadisonPaul Begovatz - University of Wisconsin–MadisonGregory P. Barton - University of Wisconsin–MadisonSarah Erickson-Bhatt - Morgridge Institute for ResearchDavid R. Inman - University of Wisconsin–MadisonBenjamin L. Cox - Morgridge Institute for ResearchKevin W. Eliceiri - University of Wisconsin–MadisonRoberta M. Strigel - University of Wisconsin–MadisonSuzanne M. Ponik - University of Wisconsin–MadisonSean B. Fain - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- Metabolites, Vol.11(5), 274
- DOI
- 10.3390/metabo11050274
- PMID
- 33925445
- PMCID
- PMC8145849
- NLM abbreviation
- Metabolites
- eISSN
- 2218-1989
- Publisher
- Mdpi
- Number of pages
- 18
- Grant note
- UL1TR000427 / NIH/NCATS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) Department of Medical Physics at the University of Wisconsin-Madison R01 DK092454 / NIH/NIDDK; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) T32AI007635 / National Institute of Allergy and Immunological Diseases AAPM 2014 Graduate Fellowship Radiological Society of North America Research and Education Foundation GE Healthcare; General Electric P30CA014520 / UW Carbone Cancer Comprehensive Cancer Center CCSG
- Language
- English
- Date published
- 05/01/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Health, Sport, and Human Physiology
- Record Identifier
- 9984274953502771
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