Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI

Erwin Krikken, Wybe J. M. van der Kemp, Vitaliy Khlebnikov, Thijs van Dalen, Maartje Los, Hanneke W. M. van Laarhoven, Peter R. Luijten, Maurice A. A. J. van den Bosch, Dennis W. J. Klomp, Jannie P. Wijnen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. Methods: In this study we combined APT MRI and 31P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). Results: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Conclusions: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.
Original languageEnglish
Article numbere4110
JournalNMR in Biomedicine
Volume32
Issue number8
DOIs
Publication statusPublished - 2019

Cite this

Krikken, E., van der Kemp, W. J. M., Khlebnikov, V., van Dalen, T., Los, M., van Laarhoven, H. W. M., ... Wijnen, J. P. (2019). Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI. NMR in Biomedicine, 32(8), [e4110]. https://doi.org/10.1002/nbm.4110
Krikken, Erwin ; van der Kemp, Wybe J. M. ; Khlebnikov, Vitaliy ; van Dalen, Thijs ; Los, Maartje ; van Laarhoven, Hanneke W. M. ; Luijten, Peter R. ; van den Bosch, Maurice A. A. J. ; Klomp, Dennis W. J. ; Wijnen, Jannie P. / Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI. In: NMR in Biomedicine. 2019 ; Vol. 32, No. 8.
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title = "Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI",
abstract = "Purpose: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. Methods: In this study we combined APT MRI and 31P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). Results: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Conclusions: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.",
author = "Erwin Krikken and {van der Kemp}, {Wybe J. M.} and Vitaliy Khlebnikov and {van Dalen}, Thijs and Maartje Los and {van Laarhoven}, {Hanneke W. M.} and Luijten, {Peter R.} and {van den Bosch}, {Maurice A. A. J.} and Klomp, {Dennis W. J.} and Wijnen, {Jannie P.}",
year = "2019",
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Krikken, E, van der Kemp, WJM, Khlebnikov, V, van Dalen, T, Los, M, van Laarhoven, HWM, Luijten, PR, van den Bosch, MAAJ, Klomp, DWJ & Wijnen, JP 2019, 'Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI' NMR in Biomedicine, vol. 32, no. 8, e4110. https://doi.org/10.1002/nbm.4110

Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI. / Krikken, Erwin; van der Kemp, Wybe J. M.; Khlebnikov, Vitaliy; van Dalen, Thijs; Los, Maartje; van Laarhoven, Hanneke W. M.; Luijten, Peter R.; van den Bosch, Maurice A. A. J.; Klomp, Dennis W. J.; Wijnen, Jannie P.

In: NMR in Biomedicine, Vol. 32, No. 8, e4110, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI

AU - Krikken, Erwin

AU - van der Kemp, Wybe J. M.

AU - Khlebnikov, Vitaliy

AU - van Dalen, Thijs

AU - Los, Maartje

AU - van Laarhoven, Hanneke W. M.

AU - Luijten, Peter R.

AU - van den Bosch, Maurice A. A. J.

AU - Klomp, Dennis W. J.

AU - Wijnen, Jannie P.

PY - 2019

Y1 - 2019

N2 - Purpose: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. Methods: In this study we combined APT MRI and 31P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). Results: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Conclusions: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.

AB - Purpose: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. Methods: In this study we combined APT MRI and 31P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). Results: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. Conclusions: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.

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U2 - 10.1002/nbm.4110

DO - 10.1002/nbm.4110

M3 - Article

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JO - NMR in Biomedicine

JF - NMR in Biomedicine

SN - 0952-3480

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