Overhauser Enhanced Magnetic Resonance Imaging (OMRI)

奥豪瑟增强磁共振成像 (OMRI)

• 批准号: 8552703
• 负责人: murali cherukuri
• 金额: $ 51.21万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8552703
• 关键词: Aftercare; Ants; Biochemical; Bolus Infusion; Cell Nucleus; Chemicals; Correlative Study; Cytotoxin; Dependence; Dose; Hour; Hypoxia; Image; Investigation; Knowledge; Label; Magnetic Resonance Imaging; Magnetism; Maps; Measures; Metabolic; Metabolism; Mitochondria; Monitor; Mus; Nature; Phenotype; Physiology; Production; Property; Protons; Pyruvate; Radiation; Radiation therapy; Reporting; Schedule; Signal Transduction; Techniques; Testing; Time; Tracer; Tumor Cell Line; Warburg Effect; Water; Xenograft procedure; aerobic glycolysis; base; bromopyruvate; density; in vivo; molecular imaging; neoplastic cell; pancreatic neoplasm; response; treatment effect; treatment response; tumor; tumor xenograft

1) Effect of 3-bromopyruvate as ant-metabolite in treating tumor bearing miceThe anti-metabolite 3-bromopyruvate has been shown to be having anti-tumor effects by shutting down the energy production in the mitochondria. Earlier reports suggest that this is efficacious in hypoxic regions in the tumor as well. We conducted a systematic investigation using pO2 mapping and 13C imaging and found that the efficacy of 3-Bromopyruvate depends on the expression of monocarboxylate transporter-1 (MCT-1). This is the first demonstration of serial pO2 imaging and metabolic imaging using 13C pyruvate. 2) Tumor hypoxia and aerobic glycolysis of pancreatic tumor xenografts.We have examined three different pancreatic tumor cell phenotypes as xenografts in mice for their pO2 status and glycolytic erfficiency and further examine their radioresponse in vivo. The three tumor cell lines tested were Miapaca, HS766T, and Su8686. The pO2 status in terms of pO2 was SU8686>Miapaca>HS766T. The glycolytic efficiency, consistent with Warburg effect was as follows: HS766T>MiaPaca>Su8686. Such correlative studies between tumor pO2 status and glycolytic activity in vivo are being demonstrated for the first time. With a priori knowledge of tumor pO2 status of these three pancreatic tumor cell phenotypes, we then evaluated the radioresponse in vivo. The radiation response showed that tumor pO2 is a crucial determinant in response to therapy. We found that Su 86.86 to be the most responsive and HS766T to be the least and Miapaca to be intermediate. We also found that pyruvate administration as a bolus dose enhanced the efficacy of a hypoxic cytotoxin TH-302 in Hs766T and Miapaca but not in Su8686. 3) Sequential imaging of tumor pO2 and glycolytic activity.We are conducting sequential EPR imaging of tumor bearing mice for tumor pO2 using EPRI and glycolytic activity using metabolic MRI using 13C pyruvate as a tracer and looking at changes in these properties after radiation treatment. We find that immediately after a 3 Gy exposure, the hypoxic fraction increases but 24 hours later there is a tumor reoxygenation. This study will provide guidance to schedule fractionated radiotherapy to make use of temporal window of increased tumor pO2.

1)3-溴丙酮酸作为抗代谢物在治疗荷瘤小鼠中的作用抗代谢物3-溴丙酮酸已被证明通过关闭线粒体中的能量产生而具有抗肿瘤作用。早期的报道表明，这在肿瘤的缺氧区域也是有效的。我们使用pO 2作图和13 C成像进行了系统研究，发现3-溴丙酮酸的疗效取决于单羧酸转运蛋白-1（MCT-1）的表达。这是首次使用13 C丙酮酸盐进行连续pO 2成像和代谢成像的演示。 2)胰腺肿瘤异种移植物的肿瘤缺氧和有氧糖酵解我们检测了三种不同胰腺肿瘤细胞表型作为小鼠异种移植物的pO 2状态和糖酵解效率，并进一步检测了它们的体内放射反应。测试的三种肿瘤细胞系是Miapaca、HS 766 T和Su 8686。根据pO 2，pO 2状态为SU 8686 Miapaca HS 766 T。与瓦尔堡效应一致的糖酵解效率如下：肿瘤pO 2状态和体内糖酵解活性之间的这种相关性研究是首次得到证实。有了这三种胰腺肿瘤细胞表型的肿瘤pO 2状态的先验知识，我们然后评估了体内放射反应。放射反应表明，肿瘤pO 2是治疗反应的关键决定因素。我们发现，苏86.86是最敏感的，HS 766 T是最少的，Miapaca是中间。我们还发现，丙酮酸作为推注剂量的管理增强了疗效的缺氧细胞毒素TH-302在Hs 766 T和Miapaca，但不是在Su 8686。3)肿瘤pO 2和糖酵解活性的顺序成像我们正在使用EPRI对荷瘤小鼠进行肿瘤pO 2的顺序EPR成像，使用代谢MRI使用13 C丙酮酸作为示踪剂进行糖酵解活性，并观察放射治疗后这些特性的变化。 我们发现，3戈伊照射后，缺氧分数立即增加，但24小时后，肿瘤复氧。本研究将为利用肿瘤pO 2升高的时间窗安排分次放疗提供指导。