. 2020 Jul 31;2(4):e200017.

doi: 10.1148/rycan.2020200017.

Hyperpolarized ¹³C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

Ramona Woitek¹, Mary A McLean¹, Andrew B Gill¹, James T Grist¹, Elena Provenzano¹, Andrew J Patterson¹, Stephan Ursprung¹, Turid Torheim¹, Fulvio Zaccagna¹, Matthew Locke¹, Marie-Christine Laurent¹, Sarah Hilborne¹, Amy Frary¹, Lucian Beer¹, Leonardo Rundo¹, Ilse Patterson¹, Rhys Slough¹, Justine Kane¹, Heather Biggs¹, Emma Harrison¹, Titus Lanz¹, Bristi Basu¹, Richard Baird¹, Evis Sala¹, Martin J Graves¹, Fiona J Gilbert¹, Jean E Abraham¹, Carlos Caldas¹, Kevin M Brindle¹, Ferdia A Gallagher¹

Affiliations

Affiliation

¹ Departments of Radiology (R.W., A.B.G., J.T.G., A.J.P., S.U., F.Z., M.L., M.C.L., S.H., A.F., L.B., L.R., E.S., M.J.G., F.J.G., F.A.G.), Oncology (J.K., H.B., E.H., B.B., R.B., J.E.A., C.C.), and Biochemistry (K.M.B.), the Cambridge Breast Cancer Research Unit (E.P., J.K., H.B., E.H., R.B., J.E.A., C.C.), University of Cambridge, Cambridge, England; Departments of Radiology (A.J.P., I.P., R.S., M.J.G., F.J.G., F.A.G.) and Histopathology (E.P.), Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England; Cancer Research UK Cambridge Centre, Cambridge, England (R.W., M.A.M., E.P., T.T., L.B., L.R., E.S., J.E.A., C.C., K.M.B., F.A.G.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria (R.W., L.B.); Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, England (M.A.M., T.T., C.C., K.M.B.); and RAPID Biomedical, Rimpar, Germany (T.L.).

PMID: 32803167
PMCID: PMC7398116
DOI: 10.1148/rycan.2020200017

Hyperpolarized ¹³C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

Ramona Woitek et al. Radiol Imaging Cancer. 2020.

. 2020 Jul 31;2(4):e200017.

doi: 10.1148/rycan.2020200017.

Authors

Affiliation

¹ Departments of Radiology (R.W., A.B.G., J.T.G., A.J.P., S.U., F.Z., M.L., M.C.L., S.H., A.F., L.B., L.R., E.S., M.J.G., F.J.G., F.A.G.), Oncology (J.K., H.B., E.H., B.B., R.B., J.E.A., C.C.), and Biochemistry (K.M.B.), the Cambridge Breast Cancer Research Unit (E.P., J.K., H.B., E.H., R.B., J.E.A., C.C.), University of Cambridge, Cambridge, England; Departments of Radiology (A.J.P., I.P., R.S., M.J.G., F.J.G., F.A.G.) and Histopathology (E.P.), Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England; Cancer Research UK Cambridge Centre, Cambridge, England (R.W., M.A.M., E.P., T.T., L.B., L.R., E.S., J.E.A., C.C., K.M.B., F.A.G.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria (R.W., L.B.); Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, England (M.A.M., T.T., C.C., K.M.B.); and RAPID Biomedical, Rimpar, Germany (T.L.).

PMID: 32803167
PMCID: PMC7398116
DOI: 10.1148/rycan.2020200017

Abstract

Purpose: To compare hyperpolarized carbon 13 (¹³C) MRI with dynamic contrast material-enhanced (DCE) MRI in the detection of early treatment response in breast cancer.

Materials and methods: In this institutional review board-approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent ¹³C MRI after injection of hyperpolarized [1-carbon 13 {¹³C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The ¹³C-labeled lactate-to-pyruvate ratio derived from hyperpolarized ¹³C MRI and the pharmacokinetic parameters transfer constant (K ^trans) and washout parameter (k _ep) derived from DCE MRI were compared before and after treatment.

Results: Exchange of the ¹³C label between injected hyperpolarized [1-¹³C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the ¹³C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean K ^trans (132%) and mean k _ep (31%), which could be incorrectly interpreted as a poor response to treatment.

Conclusion: Hyperpolarized ¹³C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.Published under a CC BY 4.0 license.

2020 by the Radiological Society of North America, Inc.

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Figures

Multinuclear hydrogen 1 and 13C MR images of the right breast at baseline (top) and after one cycle of neoadjuvant chemotherapy (bottom). (a) Coronal summed hyperpolarized [1-13C]-pyruvate and (b) [1-13C]-lactate signal overlaid on unenhanced T1-weighted images. (c) Coronal dynamic contrast-enhanced MR image obtained 150 seconds after contrast agent injection and (d) overlaid transfer constant (Ktrans) map. — **Figure 1a:**
Multinuclear hydrogen 1 and ¹³C MR images of the right breast at baseline (top) and after one cycle of neoadjuvant chemotherapy (bottom). **(a)** Coronal summed hyperpolarized [1-¹³C]-pyruvate and **(b)** [1-¹³C]-lactate signal overlaid on unenhanced T1-weighted images. **(c)** Coronal dynamic contrast-enhanced MR image obtained 150 seconds after contrast agent injection and **(d)** overlaid transfer constant (K^trans) map.

Summed 13C spectra over time after 13C-pyruvate bolus arrival in the breast. Summed spectra for (a) baseline and (b) after one cycle of neoadjuvant chemotherapy. ppm = parts per million. — **Figure 2a:**
Summed ¹³C spectra over time after ¹³C-pyruvate bolus arrival in the breast. Summed spectra for **(a)** baseline and **(b)** after one cycle of neoadjuvant chemotherapy. ppm = parts per million.

Changes in volume, 13C-lactate-to-pyruvate (Lac/Pyr) ratio, exchange rate constant (kPL), transfer constant (Ktrans), and washout parameter (kep) between baseline and follow-up imaging after one cycle (cycle 1) of neoadjuvant chemotherapy. While tumor volume and Lac/Pyr ratio decreased during treatment in this responding patient, pharmacokinetic parameters Ktrans and kep increased. Changes in Lac/Pyr ratio and kPL are based on imaging data, not spectra. The 13C MRI-based metrics were therefore more reliable than dynamic contrast material–enhanced MRI in correctly identifying this patient as a responder. Volumes of interest covering the entire tumor at the baseline and follow-up imaging were used to calculate these mean values.. — **Figure 3:**
Changes in volume, ¹³C-lactate-to-pyruvate (Lac/Pyr) ratio, exchange rate constant (k_PL), transfer constant (K^trans), and washout parameter (k_ep) between baseline and follow-up imaging after one cycle (cycle 1) of neoadjuvant chemotherapy. While tumor volume and Lac/Pyr ratio decreased during treatment in this responding patient, pharmacokinetic parameters K^trans and k_ep increased. Changes in Lac/Pyr ratio and k_PL are based on imaging data, not spectra. The ¹³C MRI-based metrics were therefore more reliable than dynamic contrast material–enhanced MRI in correctly identifying this patient as a responder. Volumes of interest covering the entire tumor at the baseline and follow-up imaging were used to calculate these mean values.^.

See this image and copyright information in PMC

References

1. Worldwide cancer data. World Cancer Research Fund Web site. https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed May 9, 2019.
1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) . Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 2018;19(1):27–39. - PMC - PubMed
1. Pennisi A, Kieber-Emmons T, Makhoul I, Hutchins L. Relevance of Pathological Complete Response after Neoadjuvant Therapy for Breast Cancer. Breast Cancer (Auckl) 2016;10:103–106. - PMC - PubMed
1. Cortazar P, Zhang L, Untch M, et al. . Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384(9938):164–172 [Published correction appears in Lancet 2019;393(10175):986.]. - PubMed
1. Fowler AM, Mankoff DA, Joe BN. Imaging Neoadjuvant Therapy Response in Breast Cancer. Radiology 2017;285(2):358–375. - PubMed

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Hyperpolarized ¹³C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

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Hyperpolarized ¹³C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

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