Sawas-Dimopoulou C, Sigalas I, Margaritis L
Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research Demokritos, AG. Paraskevi Attiki, Greece.
Nucl Med Biol. 1996 Aug;23(6):807-12. doi: 10.1016/0969-8051(96)00077-7.
An experimental mice model of maleate (MAL)-induced Fanconi syndrome has been used to test 99mTc-DTPA ability to detect hampered glomerular filtration rate (GFR) early in drug-induced Fanconi syndrome. In fact, declining GFR has been reported both in idiopathic and acquired Fanconi syndrome. The above MAL model shows urine biochemistry changes similar to those reported in patients suffering from Fanconi syndrome. Moreover, biodistribution study and whole-body autoradiographies performed after IV injection of 99mTc-DTPA in MAL and control mice show significantly delayed pharmacokinetics of the above radiopharmaceutical in a MAL dose-dependent effect. After administration of a MAL dose of 6 mM/kg BW, the 5-min biodistribution of 99mTc-DTPA, a radiopharmaceutical freely excreted by glomerular filtration, is significantly changed in all organs. In blood of MAL mice, 27.62 +/- 2.86% of the injected dose is still circulating compared to 13.67 +/- 1.22% of the injected dose in control mice, and only 1.37 +/- 0.31% of the injected dose has been excreted in urine of MAL mice compared to 24.66 +/- 4.12% of the injected dose in urine of control mice. The obtained results suggest that 99mTc-DTPA may be efficient both in the early detection of abnormal GFR in acquired Fanconi syndrome after application of a nephrotoxic treatment, and in the follow-up of patients in recovery phase after discontinuation of the therapy.
已使用马来酸盐（MAL）诱导的范科尼综合征实验小鼠模型来测试99mTc-DTPA在药物诱导的范科尼综合征早期检测肾小球滤过率（GFR）受损的能力。事实上，特发性和获得性范科尼综合征均有GFR下降的报道。上述MAL模型显示出与范科尼综合征患者报道的尿液生化变化相似。此外，在MAL小鼠和对照小鼠静脉注射99mTc-DTPA后进行的生物分布研究和全身放射自显影显示，上述放射性药物的药代动力学在MAL剂量依赖性效应中显著延迟。给予6 mM/kg体重的MAL剂量后，肾小球滤过自由排泄的放射性药物99mTc-DTPA在5分钟时的生物分布在所有器官中均发生显著变化。在MAL小鼠的血液中，注射剂量的27.62±2.86%仍在循环，而对照小鼠中为注射剂量的13.67±1.22%；在MAL小鼠的尿液中，仅1.37±0.31%的注射剂量已排出，而对照小鼠尿液中为注射剂量的24.66±4.12%。所得结果表明，99mTc-DTPA在肾毒性治疗后获得性范科尼综合征异常GFR的早期检测以及治疗中断后恢复期患者的随访中可能都是有效的。
