Induction of an experimental Fanconi syndrome in mice: its effect on the glomerular filtration function studied by 99mTc-DTPA.
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.
Sawas-Dimopoulou
C
C
Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research Demokritos, AG. Paraskevi Attiki, Greece.
Sigalas
I
I
Margaritis
L
L
D000818:Animals; D001345:Autoradiography; D004195:Disease Models, Animal; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000503:physiopathology* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000503:physiopathology*; D008298:Maleates; D051379:Mice; D008815:Mice, Inbred Strains; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics / Q000652:urine; D014018:Tissue Distribution; D014915:Whole-Body Counting
D008298:Maleates; C030272:maleic acid; D016284:Technetium Tc 99m Pentetate