MITOCHONDRIAL REDOX IMAGING AND CEST-MRI OF BREAST CANCER

这个子项目是利用这些资源的众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Low temperature NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imaging or "redox scanning" has been developed to image the in vivo mitochondrial redox states of tissues on the basis of the redox ratios (Fp/NADH or Fp/(NADH+Fp)) and may be useful for clinical diagnosis and treatment of diseases given the central role of mitochondria in cellular metabolism, apoptosis and signaling transductions. Previously we have applied this technique to a panel of human melanoma mouse xenografts with different metastatic potential and identify Fp redox ratio correlates highly significantly with the aggressiveness of these melanomas. We have also shown that T1rho-MR, sensitive to proton exchange rate, may differentiate three melanoma mouse xenografts. In this subproject we aim to achieve 1) redox imaging of breast tumor mouse xenografts with different metastatic potentials; 2) correlation of 3D redox imaging with CEST-MRI (Chemical Exchange Saturation Transfer-MRI, also sensitive to H exchange with chemical shift specificity) of breast tumors in mouse xenografts; 3) simultaneous imaging of glucose uptake and mitochondrial redox state in tissue; 4) identification of imaging biomarkers that can differentiate between aggressive and indolent breast tumors.