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

小鼠异种移植物中人类前列腺癌的 MR-CEST 和氧化还原成像

• 批准号: 8362021
• 负责人: LIN LI
• 金额: $ 0.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362021
• 关键词: Adverse effects; Biological Markers; Biopsy Specimen; Cancer Patient; Cell Line; Chemicals; Classification; Clinical; Flavoproteins; Fluorescence; Funding; Grant; Human; Image; In Vitro; Indolent; MCF7 cell; Magnetic Resonance; Magnetic Resonance Imaging; Malignant neoplasm of prostate; Measures; Melanoma Cell; Methods; Mitochondria; Mus; NADH; National Center for Research Resources; Neoplasm Metastasis; Nicotinamide adenine dinucleotide; Oxidation-Reduction; Patients; Physicians; Principal Investigator; Protons; Recording of previous events; Research; Research Infrastructure; Resources; Scanning; Signal Transduction; Source; Specificity; Staging; Therapeutic; Tissues; Tumor Markers; United States National Institutes of Health; Water; Xenograft procedure; base; cold temperature; cost; fluorescence imaging; imaging modality; in vivo; indexing; macromolecule; malignant breast neoplasm; melanoma; mouse model; optical imaging; tumor

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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无法准确预测肿瘤是否会转移以及多久会转移。在同一阶段和级别内，某些肿瘤可能比其他肿瘤更早转移。 肿瘤转移潜力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 MR 和光学成像方法来预测人类前列腺癌在小鼠异种移植物中的侵袭性。 此前，我们获得了一组具有已知临床病史的五种黑色素瘤细胞系，在小鼠模型中测量了它们的转移潜力，并通过博伊登室法在体外测量了侵袭潜力。 特别是，低温NADH/Fp（还原型烟酰胺腺嘌呤二核苷酸/氧化黄素蛋白，包括FAD）荧光成像或“氧化还原扫描”（可翻译为活检标本）可以根据以下荧光信号测量组织的体内线粒体氧化还原状态： NADH、Fp 和 Fp 氧化还原比 (Fp/(NADH+Fp))。氧化还原扫描表明，肿瘤核心中的 Fp 氧化还原比与五种黑色素瘤异种移植物的侵袭性指数显着相关，涵盖了整个转移潜力范围。此外，氧化还原成像生物标志物已被证明可以区分惰性 MCF-7 乳腺癌小鼠异种移植物和 MDA-MB-231 侵袭性异种移植物。 T1rho-MRI 对水和大分子之间的质子交换敏感。此前我们已成功使用 T1rho 区分三种具有不同侵袭性的黑色素瘤异种移植物。 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与 CEST-MRI 相结合来表征这些前列腺癌异种移植物，并识别肿瘤侵袭性的成像标记。