MITOCHONDRIAL REDOX IMAGING AND CEST-MRI OF BREAST CANCER

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 低温NADH/FP(还原型烟酰胺腺嘌呤二核苷酸/氧化黄素蛋白)荧光成像或氧化还原扫描是基于氧化还原比(FP/NADH或FP/(NADH+FP))对体内组织线粒体氧化还原状态的成像，鉴于线粒体在细胞代谢、细胞凋亡和信号转导中的中心作用，低温NADH/FP可能有助于临床诊断和治疗疾病。此前，我们已经将这项技术应用于一组具有不同转移潜力的人黑色素瘤小鼠移植瘤，并发现FP氧化还原比率与这些黑色素瘤的侵袭性高度相关。我们还表明，对质子交换率敏感的T1rho-MR可以区分三种黑色素瘤小鼠移植瘤。在这个子项目中，我们的目标是实现1)具有不同转移潜能的乳腺癌小鼠移植瘤的氧化还原成像；2)3D氧化还原成像与CEST-MRI(化学交换饱和转移磁共振成像，也对氢交换具有化学位移特异性)的关联；3)组织中葡萄糖摄取和线粒体氧化还原状态的同时成像；4)识别可以区分侵袭性和惰性乳腺肿瘤的成像生物标志物。

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.