Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential
This study uses dynamic hyperpolarized [1-<sup>13</sup>C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, <i>n</i> = 7) and metastatically dormant (4T07, <i>n</i> = 7) murine...
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| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/5/274 |
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| author | Erin B. Macdonald Paul Begovatz Gregory P. Barton Sarah Erickson-Bhatt David R. Inman Benjamin L. Cox Kevin W. Eliceiri Roberta M. Strigel Suzanne M. Ponik Sean B. Fain |
| author_facet | Erin B. Macdonald Paul Begovatz Gregory P. Barton Sarah Erickson-Bhatt David R. Inman Benjamin L. Cox Kevin W. Eliceiri Roberta M. Strigel Suzanne M. Ponik Sean B. Fain |
| author_sort | Erin B. Macdonald |
| collection | DOAJ |
| description | This study uses dynamic hyperpolarized [1-<sup>13</sup>C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, <i>n</i> = 7) and metastatically dormant (4T07, <i>n</i> = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (k<sub>PL</sub>) and lactate-to-pyruvate area-under-the-curve ratio (AUC<sub>L/P</sub>) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing k<sub>PL</sub> (<i>p</i> = 0.17) and AUC<sub>L/P</sub> (<i>p</i> = 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-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUC<sub>L/P</sub> was significantly correlated with tumor LDH activity (<i>ρ</i><sub>spearman</sub> = 0.621, <i>p</i> = 0.027) and blood glucose levels (<i>ρ</i><sub>spearman</sub> = −0.474, <i>p</i> = 0.042). k<sub>PL</sub> displayed a similar, non-significant trend for LDH activity (<i>ρ</i><sub>spearman</sub> = 0.480, <i>p</i> = 0.114) and blood glucose levels (<i>ρ</i><sub>spearman</sub> = −0.414, <i>p</i> = 0.088). Neither k<sub>PL</sub> nor AUC<sub>L/P</sub> were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUC<sub>L/P</sub> and tumor LDH activity indicates the potential of AUC<sub>L/P</sub> 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. |
| first_indexed | 2024-03-10T11:54:41Z |
| format | Article |
| id | doaj.art-0e5901338ece4ce1a49ae64e5a7b8b76 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T11:54:41Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-0e5901338ece4ce1a49ae64e5a7b8b762023-11-21T17:21:06ZengMDPI AGMetabolites2218-19892021-04-0111527410.3390/metabo11050274Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic PotentialErin B. Macdonald0Paul Begovatz1Gregory P. Barton2Sarah Erickson-Bhatt3David R. Inman4Benjamin L. Cox5Kevin W. Eliceiri6Roberta M. Strigel7Suzanne M. Ponik8Sean B. Fain9Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USAMorgridge Institute for Research, 330 N. Orchard St., Madison, WI 53715, USADepartment of Cell and Regenerative Biology, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Cell and Regenerative Biology, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USADepartment of Medical Physics, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USAThis study uses dynamic hyperpolarized [1-<sup>13</sup>C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, <i>n</i> = 7) and metastatically dormant (4T07, <i>n</i> = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (k<sub>PL</sub>) and lactate-to-pyruvate area-under-the-curve ratio (AUC<sub>L/P</sub>) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing k<sub>PL</sub> (<i>p</i> = 0.17) and AUC<sub>L/P</sub> (<i>p</i> = 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-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUC<sub>L/P</sub> was significantly correlated with tumor LDH activity (<i>ρ</i><sub>spearman</sub> = 0.621, <i>p</i> = 0.027) and blood glucose levels (<i>ρ</i><sub>spearman</sub> = −0.474, <i>p</i> = 0.042). k<sub>PL</sub> displayed a similar, non-significant trend for LDH activity (<i>ρ</i><sub>spearman</sub> = 0.480, <i>p</i> = 0.114) and blood glucose levels (<i>ρ</i><sub>spearman</sub> = −0.414, <i>p</i> = 0.088). Neither k<sub>PL</sub> nor AUC<sub>L/P</sub> were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUC<sub>L/P</sub> and tumor LDH activity indicates the potential of AUC<sub>L/P</sub> 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.https://www.mdpi.com/2218-1989/11/5/274breast cancermetastatic potentialmetabolismMRSIhyperpolarizedcarbon-13 |
| spellingShingle | Erin B. Macdonald Paul Begovatz Gregory P. Barton Sarah Erickson-Bhatt David R. Inman Benjamin L. Cox Kevin W. Eliceiri Roberta M. Strigel Suzanne M. Ponik Sean B. Fain Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential Metabolites breast cancer metastatic potential metabolism MRSI hyperpolarized carbon-13 |
| title | Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential |
| title_full | Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential |
| title_fullStr | Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential |
| title_full_unstemmed | Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential |
| title_short | Hyperpolarized <sup>13</sup>C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential |
| title_sort | hyperpolarized sup 13 sup c magnetic resonance spectroscopic imaging of pyruvate metabolism in murine breast cancer models of different metastatic potential |
| topic | breast cancer metastatic potential metabolism MRSI hyperpolarized carbon-13 |
| url | https://www.mdpi.com/2218-1989/11/5/274 |
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