MR AND REDOX IMAGING OF HUMAN MELANOMA MOUSE XENOGRAFTS

人类黑色素瘤小鼠异种移植物的 MR 和氧化还原成像

• 批准号: 8169089
• 负责人: LIN LI
• 金额: $ 3.47万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169089
• 关键词: Adverse effects; Biological Markers; Biopsy Specimen; Breast; Cancer Patient; Cell Line; Classification; Clinic; Clinical; Computer Retrieval of Information on Scientific Projects Database; Flavoproteins; Fluorescence; Funding; Goals; Grant; Human; Image; In Vitro; Institution; Magnetic Resonance Imaging; Measurable; Measures; Melanoma Cell; Methods; Mitochondria; Mus; NADH; Neoplasm Metastasis; Nicotinamide adenine dinucleotide; Oxidation-Reduction; Patients; Permeability; Physicians; Prostate Lymphoma; Recording of previous events; Relaxation; Research; Research Personnel; Resources; Scanning; Signal Transduction; Source; Staging; Testing; Therapeutic; Time; Tissues; Translating; United States National Institutes of Health; Water; Xenograft procedure; base; blood perfusion; cancer type; cold temperature; fluorescence imaging; imaging modality; in vivo; macromolecule; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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 our goal is to develop MR and optical imaging methods to predict the aggressiveness of human melanomas in mouse xenografts. 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. We hope to establish some imaging biomarkers utilizing this panel of human melanomas with different levels of aggressiveness. These biomarkers can then be tested on other types of cancers such as breast, prostate, lymphoma etc and eventually translated into clinic. We have selected two MRI methods, i.e., DCE-MRI and T1¿-MRI and the low temperature NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins including FAD) fluorescence imaging or "redox scanning" (measurable on biopsy specimens) for this purpose. DCE-MRI can measure the blood perfusion and vessel permeability in the tumor. T1¿-MRI quantifies the T1¿ relaxation time constants reflecting the interaction between water and macromolecules. Redox scanning 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)).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 大多数癌症患者死于转移。目前的肿瘤分类基于分期和转移。 级别无法准确预测肿瘤是否会转移以及多久会转移。 同一阶段和级别，某些肿瘤可能比其他肿瘤更早转移。 肿瘤转移潜力的评估可以帮助医生选择适当的侵袭性 治疗肿瘤的方法，同时最大限度地减少对患者的副作用。 项目我们的目标是开发 MR 和光学成像方法来预测 我们获得了一组五种黑色素瘤细胞系。 具有已知的临床病史，在小鼠模型和侵入性模型中测量了它们的转移潜力 我们希望建立一些通过博伊登室法体外测量的电位。 利用这组具有不同水平的人类黑色素瘤的成像生物标志物 然后可以在其他类型的癌症上测试这些生物标志物，例如乳腺癌、 前列腺癌、淋巴瘤等并最终转化为临床。 我们选择了两种 MRI 方法，即 DCE-MRI 和 T1¿ -MRI和低温 NADH/Fp（还原型烟酰胺腺嘌呤二核苷酸/氧化黄素蛋白，包括 FAD） 用于此目的的荧光成像或“氧化还原扫描”（可在活检标本上测量）。 DCE-MRI 可以测量肿瘤 T1 中的血液灌注和血管通透性。 -MRI 量化 T1¿弛豫时间常数反映了水与水之间的相互作用 大分子氧化还原扫描可以测量组织的体内线粒体氧化还原状态。 基于 NADH、Fp 和 Fp 氧化还原比 (Fp/(NADH+Fp)) 的荧光信号。