Breast Cancer Redox Heterogeneity Detectable with Chemical Exchange Saturation Transfer (CEST) MRI

Kejia Cai, He N. Xu, Anup Singh, Lily Moon, Mohammad Haris, Ravinder Reddy, Lin Z. Li

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Tissue redox state is an important mediator of various biological processes in health and diseases such as cancer. Previously, we discovered that the mitochondrial redox state of ex vivo tissues detected by redox scanning (an optical imaging method) revealed interesting tumor redox state heterogeneity that could differentiate tumor aggressiveness. Because the noninvasive chemical exchange saturation transfer (CEST) MRI can probe the proton transfer and generate contrasts from endogenous metabolites, we aim to investigate if the in vivo CEST contrast is sensitive to proton transfer of the redox reactions so as to reveal the tissue redox states in breast cancer animal models.

Procedures: CEST MRI has been employed to characterize tumor metabolic heterogeneity and correlated with the redox states measured by the redox scanning in two human breast cancer mouse xenograft models, MDA-MB-231 and MCF-7. The possible biological mechanism on the correlation between the two imaging modalities was further investigated by phantom studies where the reductants and the oxidants of the representative redox reactions were measured.

Results: The CEST contrast is found linearly correlated with NADH concentration and the NADH redox ratio with high statistical significance, where NADH is the reduced form of nicotinamide adenine dinucleotide. The phantom studies showed that the reductants of the redox reactions have more CEST contrast than the corresponding oxidants, indicating that higher CEST effect corresponds to the more reduced redox state.

Conclusions: This preliminary study suggests that CEST MRI, once calibrated, might provide a novel noninvasive imaging surrogate for the tissue redox state and a possible diagnostic biomarker for breast cancer in the clinic.

Original languageEnglish
Pages (from-to)670-679
Number of pages10
JournalMolecular Imaging and Biology
Volume16
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Oxidation-Reduction
Breast Neoplasms
NAD
Reducing Agents
Oxidants
Protons
Neoplasms
Biological Phenomena
Optical Imaging
Heterografts
Animal Models
Biomarkers

Keywords

  • Cancer metabolism
  • CEST
  • Intratumor heterogeneity
  • NADH
  • Redox state

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Breast Cancer Redox Heterogeneity Detectable with Chemical Exchange Saturation Transfer (CEST) MRI. / Cai, Kejia; Xu, He N.; Singh, Anup; Moon, Lily; Haris, Mohammad; Reddy, Ravinder; Li, Lin Z.

In: Molecular Imaging and Biology, Vol. 16, No. 5, 2014, p. 670-679.

Research output: Contribution to journalArticle

Cai, Kejia ; Xu, He N. ; Singh, Anup ; Moon, Lily ; Haris, Mohammad ; Reddy, Ravinder ; Li, Lin Z. / Breast Cancer Redox Heterogeneity Detectable with Chemical Exchange Saturation Transfer (CEST) MRI. In: Molecular Imaging and Biology. 2014 ; Vol. 16, No. 5. pp. 670-679.
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AB - Purpose: Tissue redox state is an important mediator of various biological processes in health and diseases such as cancer. Previously, we discovered that the mitochondrial redox state of ex vivo tissues detected by redox scanning (an optical imaging method) revealed interesting tumor redox state heterogeneity that could differentiate tumor aggressiveness. Because the noninvasive chemical exchange saturation transfer (CEST) MRI can probe the proton transfer and generate contrasts from endogenous metabolites, we aim to investigate if the in vivo CEST contrast is sensitive to proton transfer of the redox reactions so as to reveal the tissue redox states in breast cancer animal models.Procedures: CEST MRI has been employed to characterize tumor metabolic heterogeneity and correlated with the redox states measured by the redox scanning in two human breast cancer mouse xenograft models, MDA-MB-231 and MCF-7. The possible biological mechanism on the correlation between the two imaging modalities was further investigated by phantom studies where the reductants and the oxidants of the representative redox reactions were measured.Results: The CEST contrast is found linearly correlated with NADH concentration and the NADH redox ratio with high statistical significance, where NADH is the reduced form of nicotinamide adenine dinucleotide. The phantom studies showed that the reductants of the redox reactions have more CEST contrast than the corresponding oxidants, indicating that higher CEST effect corresponds to the more reduced redox state.Conclusions: This preliminary study suggests that CEST MRI, once calibrated, might provide a novel noninvasive imaging surrogate for the tissue redox state and a possible diagnostic biomarker for breast cancer in the clinic.

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