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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 大多数癌症患者死于转移。基于阶段和等级的当前肿瘤分类无法准确预测肿瘤是否会转移。在同一阶段和等级中，某些肿瘤可能比其他肿瘤更早地转移。 肿瘤转移潜力的生物标志物可以帮助医生选择治疗方法的适当侵袭性，以治疗肿瘤，同时最大程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，以预测小鼠异种移植物中人类前列腺癌的侵略性。 以前，我们已经获得了一组具有已知临床病史的黑色素瘤细胞系，它们在小鼠模型中测量的转移电位和通过Boyden室法在体外测得的侵入性潜力。 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））。氧化还原扫描表明，肿瘤核心的FP氧化还原比与五种黑色素瘤异种移植物的侵略指数显着相关，这些指标跨越了转移的全部范围。另外，氧化还原成像生物标志物已被证明可以区分与MDA-MB-231侵略性的MCF-7乳腺癌小鼠异种移植物。 T1rho-MRI对水和大分子之间的质子交换敏感。以前，我们成功地使用T1RHO以不同的侵略性区分了三种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，对质子交换也敏感，但具有更高的化学移位特异性。在这个项目中，我们将使用氧化还原扫描与CEST-MRI结合使用，以表征前列腺癌的这些异种移植物，并确定肿瘤侵袭性的成像标记。