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

本研究的目的是利用回旋加速器生产的、寿命短的 放射性核素~(13)N研究标记L-氨基的体内代谢 小鼠肿瘤中敏感或耐药的酸和氨 谷氨酰胺酶或天冬酰胺酶疗法。这些N-13标记的代谢物 血液和肿瘤匀浆中的放射性药物将被检测 使用反相和离子交换层析分析。 N-13氨基和L-(酰胺-N-13)谷氨酰胺的组织分布研究 已经在对照和谷氨酰胺酶7A治疗的肉瘤-180中进行了 (谷氨酰胺酶敏感)和里奇韦成骨肉瘤(谷氨酰胺酶 抗性)小鼠。似乎没有任何显著的差异 N-13氨基或谷氨酰胺的组织分布 谷氨酰胺酶处理组和对照组。 已经对肿瘤和血液匀浆进行了代谢命运研究 N-13氨水或N-13谷氨酰胺注射后1、5和10分钟 对谷氨酰胺酶敏感和耐药的荷瘤小鼠进行治疗。这个 N-13标记在给药后的代谢去向是 主要是N-13尿素随浓度随时间增加而增加 在酸性代谢物和酸性氨基酸中含量较少。不是 标记尿素(只是一种未知的辅洗脱液)是在体外研究中形成的。 其中S肿瘤切片与N-13氨水孵育，提示 体内研究中肿瘤中形成的N-13尿素不是由于 肿瘤中的从头合成。对代谢命运进行的研究 谷氨酰胺酶治疗肉瘤-180肿瘤和血液匀浆的研究进展 动物在注射N-13氨后似乎没有明显的 与未经治疗的动物不同。(B)

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)