Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer
Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/int...
| Главные авторы: | , , , , , , , , , , , , , , , , , , , , , |
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| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
Springer Nature
2022
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| _version_ | 1826307463053312000 |
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| author | Sushentsev, N McLean, MA Warren, AY Benjamin, AJV Brodie, C Frary, A Gill, AB Jones, J Kaggie, JD Lamb, BW Locke, MJ Miller, JL Mills, IG Priest, AN Robb, FJL Shah, N Schulte, RS Graves, MJ Gnanapragasam, VJ Brindle, KM Barrett, T Gallagher, FA |
| author_facet | Sushentsev, N McLean, MA Warren, AY Benjamin, AJV Brodie, C Frary, A Gill, AB Jones, J Kaggie, JD Lamb, BW Locke, MJ Miller, JL Mills, IG Priest, AN Robb, FJL Shah, N Schulte, RS Graves, MJ Gnanapragasam, VJ Brindle, KM Barrett, T Gallagher, FA |
| author_sort | Sushentsev, N |
| collection | OXFORD |
| description | Hyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments. |
| first_indexed | 2024-03-07T07:03:30Z |
| format | Journal article |
| id | oxford-uuid:99b6f8d1-76d4-4445-9502-a38233ec7f3d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:03:30Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:99b6f8d1-76d4-4445-9502-a38233ec7f3d2022-04-11T11:18:19ZHyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:99b6f8d1-76d4-4445-9502-a38233ec7f3dEnglishSymplectic ElementsSpringer Nature2022Sushentsev, NMcLean, MAWarren, AYBenjamin, AJVBrodie, CFrary, AGill, ABJones, JKaggie, JDLamb, BWLocke, MJMiller, JLMills, IGPriest, ANRobb, FJLShah, NSchulte, RSGraves, MJGnanapragasam, VJBrindle, KMBarrett, TGallagher, FAHyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments. |
| spellingShingle | Sushentsev, N McLean, MA Warren, AY Benjamin, AJV Brodie, C Frary, A Gill, AB Jones, J Kaggie, JD Lamb, BW Locke, MJ Miller, JL Mills, IG Priest, AN Robb, FJL Shah, N Schulte, RS Graves, MJ Gnanapragasam, VJ Brindle, KM Barrett, T Gallagher, FA Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer |
| title | Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer |
| title_full | Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer |
| title_fullStr | Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer |
| title_full_unstemmed | Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer |
| title_short | Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer |
| title_sort | hyperpolarised 13c mri identifies the emergence of a glycolytic cell population within intermediate risk human prostate cancer |
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