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)).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 大多数癌症患者死于转移。目前肿瘤的分期和分级 分级不能准确预测肿瘤是否转移以及多久转移。内 相同的分期和分级，有些肿瘤可能比其他肿瘤转移早。 生物标志物 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，同时尽量减少对患者的副作用。在这 我们的目标是开发MR和光学成像方法来预测 小鼠异种移植物中的人黑素瘤。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，在小鼠模型中测量其转移潜力， 通过Boyden室法在体外测量的电势。 我们希望建立一些 利用这组具有不同水平的黑色素瘤的成像生物标志物， 侵略性这些生物标志物可以用于其他类型的癌症，如乳腺癌， 前列腺，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与低温 NADH/Fp（还原型烟酰胺腺嘌呤二核苷酸/氧化型黄素蛋白，包括FAD） 荧光成像或“氧化还原扫描”（可在活检标本上测量）。 DCE-MRI可以测量肿瘤内的血液灌注和血管通透性。T1-MRI 量化了反映水和水之间相互作用的T1？弛豫时间常数， 大分子氧化还原扫描可以测量体内组织的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。