MRI as a Potential Imaging Biomarker of Mitochondrial Metabolic State of Breast Cancer
Introduction: Tumor metabolism has become an active area of research recently. Abnormalities in mitochondrial metabolic state including redox state are found to be important factors in tumor progression. Previous work has shown mitochondrial redox state measured with redox scanning in human melanoma and breast cancer mouse xenografts can predict the tumor metastatic potential or aggressiveness [1,2] We aim to investigate if non invasive MRI methods could serve as surrogate metabolic/functional imaging biomarkers for tumor metastatic potential. The chemical exchange saturation transfer (CEST) effect from amide and hydroxyl protons have previously been exploited to measure pH [3] and liver glycogen [4] CEST contrast using high magnitude of saturating RF pulse can be used to map fast exchanging free amino acids, such as brain glutamate (Glu) [5] Glu also promotes cancer proliferation, migration and invasion of tumor cells [6] As one of the major metabolites [8] in breast cancer exhibiting CEST effect, Glu is known to be connected with mitochondrial redox reactions through a ketoglutarate in the TCA cycle. Therefore, we hypothesize that CEST effect from breast cancer amino acids (especially Glu) may be used as a non invasive biomarker of mitochondrial metabolic state for predicting cancer metastatic potential.