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

Cai, Kejia; Xu, He; Singh, Anup; Moon, Lily; Haris, Mohammad; Reddy, Ravinder; Li, Lin
October 2014
Molecular Imaging & Biology;Oct2014, Vol. 16 Issue 5, p670
Academic Journal
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.


Related Articles

  • Metabolism: In need of a NADPH rush? McCarthy, Nicola // Nature Reviews Cancer;Jun2012, Vol. 12 Issue 6, p374 

    The article discusses research on the need for the conservation of NADPH to allow redox reactions, which references the study "NADPH homeostasis to promote tumour cell survival during energy stress," by S. M. Jeon and colleagues in the May 9, 2012 issue of "Nature."

  • Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices. Somogyi, Anna; Horvai, George; Csala, Miklós; Tóth, Blanka // Periodica Polytechnica: Chemical Engineering;2016, Vol. 60 Issue 4, p218 

    Some of the main electron carriers in the metabolism are mono- or dinucleotides and they play crucial roles in maintaining a balanced redox homeostasis of cells, and in coupling many anabolic and catabolic reactions. Altered cellular redox status can be an indicator of various metabolic...

  • Structure modeling and inhibitor prediction of NADP oxidoreductase enzyme from Methanobrevibacter smithii. Sharma, Ashwani; Chaudhary, Prem Prashant; Sirohi, Sunil Kumar; Saxena, Jyoti // Bioinformation;2011, Vol. 6 Issue 1, p15 

    The F420-dependent NADP oxidoreductase enzyme from Methanobrevibacter smithii catalyzes the important electron transfer step during methanogenesis. Therefore, it may act as potential target for blocking the process of methane formation. Its protein sequence is available in GenBank (accession...

  • Dynamics of NAD-metabolism: everything but constant. Opitz, Christiane A.; Heiland, Ines // Biochemical Society Transactions;Dec2015, Vol. 43 Issue 6, p1127 

    NAD, as well as its phosphorylated form, NADP, are best known as electron carriers and co-substrates of various redox reactions. As such they participate in approximately one quarter of all reactions listed in the reaction database KEGG. In metabolic pathway analysis, the total amount of NAD is...

  • A comparative transcriptomic, fluxomic and metabolomic analysis of the response of Saccharomyces cerevisiae to increases in NADPH oxidation. Celton, Magalie; Sanchez, Isabelle; Goelzer, Anne; Fromion, Vincent; Camarasa, Carole; Dequin, Sylvie // BMC Genomics;2012, Vol. 13 Issue 1, p317 

    Background: Redox homeostasis is essential to sustain metabolism and growth. We recently reported that yeast cells meet a gradual increase in imposed NADPH demand by progressively increasing flux through the pentose phosphate (PP) and acetate pathways and by exchanging NADH for NADPH in the...

  • Perturbation of Human Coronary Artery Endothelial Cell Redox State and NADPH Generation by Methylglyoxal. Morgan, Philip E.; Sheahan, Pamela J.; Davies, Michael J. // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Diabetes is associated with elevated plasma glucose, increased reactive aldehyde formation, oxidative damage, and glycation/glycoxidation of biomolecules. Cellular detoxification of, or protection against, such modifications commonly requires NADPH-dependent reducing equivalents (e.g. GSH). We...

  • Fibroblast-to-myofibroblast switch is mediated by NAD(P)H oxidase generated reactive oxygen species. ALILI, Lirija; SACK, Maren; PUSCHMANN, Katharina; BRENNEISEN, Peter // Bioscience Reports;2014, Vol. 34 Issue 1, p7 

    Tumour-stroma interaction is a prerequisite for tumour progression in skin cancer. Hereby, a critical step in stromal function is the transition of tumour-associated fibroblasts to MFs (myofibroblasts) by growth factors, for example TGFβ (transforming growth factor beta(). In this study, the...

  • Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer. Sauter, E.R.; Zhu, W.; Fan, X.-J.; Wassell, R.P.; Chervoneva, I.; Du Bois, G.C. // British Journal of Cancer;5/6/2002, Vol. 86 Issue 9, p1440 

    The early detection of breast cancer is the best means to minimise disease-related mortality. Current screening techniques have limited sensitivity arid specificity. Breast nipple aspirate fluid can be obtained noninvasively and contains proteins secreted from ductal and Iobular epithelia....

  • Loss of heterozygosity at D14S62 and metastatic potential of breast cancer. O'Connell, Peter; Fischbach, Kathryn; O'Connell, P; Fischbach, K; Hilsenbeck, S; Mohsin, S K; Fuqua, S A; Clark, G M; Osborne, C K; Allred, D C // JNCI: Journal of the National Cancer Institute;08/18/99, Vol. 91 Issue 16, p1391 

    Background: In breast cancer progression, the prevalence of damage at specific genetic loci often increases with the stage of the lesion (i.e., from noninvasive to invasive to metastatic). By use of genetic markers and analysis of allelic imbalances (loss of heterozygosity [LOH]) to...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics