MR-CEST AND REDOX IMAGING OF HUMAN PROSTATE CANCER IN MOUSE XENOGRAFTS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 大多数癌症患者死于转移。目前基于分期和分级的肿瘤分类不能准确预测肿瘤是否转移以及转移的时间。在相同的分期和级别内，有些肿瘤可能比其他肿瘤更早转移。 肿瘤转移潜能的生物标志物可以帮助医生选择适当的治疗方法来治疗肿瘤，同时最大限度地减少对患者的副作用。在这个项目中，我们将开发磁共振和光学成像方法来预测小鼠异种移植的人前列腺癌的侵袭性。 以前，我们已经获得了一组五个黑色素瘤细胞系与已知的临床病史，其转移的潜力在小鼠模型中测量和在体外通过Boyden室方法测量的侵袭潜力。 特别地，低温NADH/Fp（还原的烟酰胺腺嘌呤二核苷酸/氧化的黄素蛋白，包括FAD）荧光成像或“氧化还原扫描”（可翻译为活检样本）可以基于NADH、Fp和Fp氧化还原比（Fp/（NADH+Fp））的荧光信号测量组织的体内线粒体氧化还原状态。氧化还原扫描表明，在肿瘤核心的Fp氧化还原比与侵袭性指数的五个黑色素瘤异种移植跨越整个范围的潜在转移显着相关。此外，氧化还原成像生物标志物已显示出区分惰性MCF-7乳腺癌小鼠异种移植物与MDA-MB-231侵袭性异种移植物。T1 rho-MRI对水和大分子之间的质子交换敏感。以前，我们已经成功地使用T1 rho来区分三种具有不同侵袭性的黑素瘤异种移植物。CEST-MRI（化学交换饱和转移-MRI）是一种类似的方法，也对质子交换敏感，但具有更高的化学位移特异性。在这个项目中，我们将采用氧化还原扫描结合CEST-MRI来表征这些前列腺癌的异种移植物，并确定肿瘤侵袭性的成像标志物。

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. Most cancer patients die of metastasis. Current classification of tumors on the basis of stage and grade cannot predict accurately whether and how soon a tumor will metastasize. Within the same stage and grade, some tumors may metastasize earlier than other tumors. A biomarker of tumor metastatic potential can help physician to select proper aggressiveness of the therapeutic approaches to treat the tumor while minimizing the side effects on patients. In this project we will develop MR and optical imaging methods to predict the aggressiveness of human prostate cancer in mouse xenografts. Previously we have obtained a panel of five melanoma cell lines with known clinical history, their metastatic potential measured in mouse models and invasive potentials measured in vitro by the Boyden chamber method. In particular, low temperature NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins including FAD) fluorescence imaging or "redox scanning" (translatable to biopsy specimens) can measure the in vivo mitochondrial redox states of tissues on the basis of the fluorescence signals of NADH, Fp, and Fp redox ratios (Fp/(NADH+Fp)). Redox scanning indicated that the Fp redox ratio in the tumor core correlated significantly with the aggressiveness indices of five melanoma xenografts spanning the full range of potential to metastasis. In addition redox imaging biomarkers have been shown to differentiate between an indolent MCF-7 breast cancer mouse xenografts from an MDA-MB-231 aggressive one. T1rho-MRI is sensitive to proton exchange between water and macromolecules. Previously we have succeeded in using T1rho to differentiate three melanoma xenografts with different aggressiveness. CEST-MRI (Chemical Exchange Saturation Transfer-MRI) is a similar method also sensitive to proton exchange but with more chemical shift specificity. In this project we will employ redox scanning in combination with CEST-MRI to characterize these xenografts of prostate cancer and to identify imaging markers for tumor aggressiveness.