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METABOLISM OF N-13 AMMONIA AND L-AMINO ACIDS IN TUMORS

N-13 氨和 L-氨基酸在肿瘤中的代谢

基本信息

批准号：
3446462
负责人：
KAREN C ROSENPIRE
金额：
$ 6.08万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-02-01 至 1986-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3446462
关键词：
aminoacid metabolism ammonia asparaginase enzyme therapy glutaminase ion transport neoplasm /cancer chemotherapy neoplasm /cancer radionuclide diagnosis particle accelerators radiopharmacology radiotracer reversed phase chromatography

项目摘要

The goal of this research is to use the cyclotron-produced, short-lived radionuclide nitrogen-13 to study the in vivo metabolism of labeled L-amino acids and ammonia in murine tumors which are sensitive or resistant to glutaminase or asparaginase therapy. The metabolites of these N-13 labeled radiopharmaceuticals in blood and tumor homogenates will be determined using reverse phase and ion exchange chromatographic analyses. Tissue distribution studies using N-13 ammonia and L-(amide-N-13) glutamine have been performed in control and glutaminase 7A treated Sarcoma-180 (glutaminase sensitive) and Ridgeway Osteogenic Sarcoma (glutaminase resistant) mice. There do not appear to be any significant differences in the tissue distributions of N-13 ammonia or glutamine between the glutaminase-treated and control mice. Metabolic fate studies have been performed on tumor and blood homogenates 1, 5, and 10 min after either N-13 ammonia or N-13 glutamine administration in treated glutaminase-sensitive and -resistant tumor-bearing mice. The metabolic fate of the N-13 label after administration of either agent is primarily N-13 urea with the concentration increasing with time with smaller amounts in the acidic metabolites and in acidic amino acids. No labeled urea (only an unknown co-eluant) was formed during in vitro studies in which S-180 tumor slices were incubated with N-13 ammonia, suggesting that the N-13 urea formed in the tumor in the in vivo studies was not due to de novo synthesis in the tumor. Metabolic fate studies performed to date on Sarcoma-180 tumor and blood homogenates in glutaminase-treated animals after N-13 ammonia injection do not appear to be significantly different from untreated animals. (B)

这项研究的目标是利用回旋加速器产生的，放射性核素氮-13研究标记的L-氨基酸和氨在小鼠肿瘤中的作用，天冬酰胺酶或天冬酰胺酶治疗。这些N-13标记的代谢物将测定血液和肿瘤匀浆中的放射性药物使用反相和离子交换色谱分析。使用N-13氨和L-（酰胺-N-13）谷氨酰胺的组织分布研究已在对照组和转氨酶7A治疗的肉瘤-180中进行（转氨酶敏感）和里奇韦成骨肉瘤（转氨酶抗性）小鼠。似乎没有任何显着差异， N-13氨或谷氨酰胺的组织分布精氨酸酶处理的小鼠和对照小鼠。已对肿瘤和血液匀浆进行了代谢结局研究 N-13氨或N-13谷氨酰胺给药后1、5和10 min 在经治疗的对精氨酸酶敏感和耐药的荷瘤小鼠中。的在施用任一药剂后，N-13标记的代谢命运是主要是N-13尿素，浓度随时间增加，酸性代谢物和酸性氨基酸中的含量较少。没有在体外研究期间形成标记尿素（仅为未知共洗脱液其中S-180肿瘤切片与N-13氨一起孵育，表明在体内研究中，肿瘤中形成的N-13尿素不是由于在肿瘤中重新合成。进行代谢结局研究，肉瘤-180肿瘤和经精氨酸酶处理的血液匀浆的数据注射N-13氨后的动物似乎没有显着变化与未经处理的动物不同。（B）