Imaging breast cancer using hyperpolarized carbon-13 MRI

• Autor: Gallagher, Ferdia A. ; Woitek, Ramona ; McLean, Mary A. ; Gill, Andrew B. ; Garcia, Raquel Manzano ; Provenzano, Elena ; Riemer, Frank ; Kaggie, Joshua ; Chhabra, Anita ; Ursprung, Stephan ; Grist, James T. ; Daniels, Charlie J. ; Zaccagna, Fulvio ; Laurent, Marie-Christine ; Locke, Matthew ; Hilborne, Sarah ; Frary, Amy ; Torheim, Turid ; Boursnell, Chris ; Schiller, Amy ; Patterson, Ilse ; Slough, Rhys ; Carmo, Bruno ; Kane, Justine ; Biggs, Heather ; Harrison, Emma ; Deen, Surrin S. ; Patterson, Andrew ; Lanz, Titus ; Kingsbury, Zoya ; Ross, Mark ; Basu, Bristi ; Baird, Richard ; Lomas, David J. ; Sala, Evis ; Wason, James ; Rueda, Oscar M. ; Chin, Suet-Feung ; Wilkinson, Ian B. ; Graves, Martin J. ; Abraham, Jean E. ; Gilbert, Fiona J. ; Caldas, Carlos ; Brindle, Kevin M.
• Assuntos: Biological Sciences ; Breast cancer ; Breast Neoplasms - diagnostic imaging ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Carbon 13 ; Carbon Isotopes - chemistry ; Carbon Isotopes - metabolism ; Carcinoma ; ErbB-2 protein ; Estrogen receptors ; Estrogens ; Exchanging ; Feasibility ; Female ; Gene sequencing ; Heterogeneity ; Humans ; Hypoxia ; Hypoxia-inducible factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-inducible factor 1a ; Immunohistochemistry ; Invasiveness ; L-Lactate dehydrogenase ; L-Lactate Dehydrogenase - genetics ; L-Lactate Dehydrogenase - metabolism ; Lactate dehydrogenase ; Lactic acid ; Magnetic resonance imaging ; Magnetic Resonance Imaging - instrumentation ; Magnetic Resonance Imaging - methods ; Magnetic resonance spectroscopy ; Medical imaging ; Metabolism ; Monocarboxylic Acid Transporters - genetics ; Monocarboxylic Acid Transporters - metabolism ; Muscle Proteins - genetics ; Muscle Proteins - metabolism ; Progesterone ; Pyruvic acid ; Pyruvic Acid - chemistry ; Pyruvic Acid - metabolism ; Ribonucleic acid ; RNA ; Symporters - genetics ; Symporters - metabolism ; Tumors
• É parte de: Proceedings of the National Academy of Sciences - PNAS, 2020-01, Vol.117 (4), p.2092-2098
• Notas: ObjectType-Article-2
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  Edited by Matthew G. Vander Heiden, Charles Koch Institute, Massachusetts Institute of Technology, and accepted by Editorial Board Member Tak W. Mak November 26, 2019 (received for review August 12, 2019)
  Author contributions: F.A.G., R.W., M.A.M., F.R., A.C., S.U., J.T.G., S.S.D., B.B., R.B., D.J.L., E.S., S.-F.C., I.B.W., M.J.G., J.E.A., F.J.G., C.C., and K.M.B. designed research; F.A.G., R.W., M.A.M., A.B.G., F.R., J.K., S.U., F.Z., M.-C.L., M.L., S.H., A.F., A.S., I.P., R.S., B.C., J.K., H.B., E.H., J.E.A., C.C., and K.M.B. performed research; M.A.M., A.P., T.L., M.J.G., and K.M.B. contributed new reagents/analytic tools; R.W., M.A.M., A.B.G., R.M.G., E.P., S.U., J.T.G., C.J.D., T.T., C.B., A.P., Z.K., M.R., J.W., O.M.R., S.-F.C., and M.J.G. analyzed data; and F.A.G., R.W., M.A.M., R.M.G., S.U., E.S., C.C., and K.M.B. wrote the paper.
  1F.A.G. and R.W. contributed equally to this work.
  
• Descrição: Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2−), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2− invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.
  
• Editor: United States: National Academy of Sciences
  
• Idioma: Inglês