title: The utility of (99m)Tc-DMSA and Tc(99m)-EC scintigraphy for early diagnosis of ifosfamide induced nephrotoxicity.
abstract: A serious undesired effect of certain cytostatics is their nephrotoxicity. In this study, we investigated the toxic effects of ifosfamide and cisplatin by clinical and biochemical parameters in relation to (99m)Tc-dimercaptosuccinic acid ((99m)Tc-DMSA) and Tc(99m)N, N-ethylenedicysteine (EC) renal scintigraphy. The indicators were urinary beta2-microglobulin levels, tubular resorption of phosphate, urinary protein and glucose excretion, glomerular filtration rate, urinary pH and osmolarity. Thirteen paediatric patients (seven boys and six girls), aged 2-16 years, were investigated. Five patients received only cisplatin, six patients were treated with ifosfamide and cisplatin and two with ifosfamide and carboplatin for various malignancies. All except three patients had normal DMSA uptake (median, 19; range, 16-29%) prior to chemotherapy. The reduction in DMSA uptake was unilateral due to tumour invasion in those three patients. Following chemotherapy, DMSA uptake showed reduction in five patients with or without clinical nephrotoxicity. The observed pattern was decreased renal uptake and elevated bladder activity. Three patients with decreased DMSA uptake had normal tubular maximum phosphate reabsorption, which suggested subclinical injury. Decrease in DMSA uptake and tubular phosphate reabsorption (TPR) was detected simultaneously in two patients. No abnormalities were seen on Tc(99m)-EC scintigraphy to suggest nephrotoxicity in our investigation. However, Tc(99m)-EC clearly demonstrated a reduction in split renal function in children with tumour invasion. In summary, we found that ifosfamide induced tubular injury can be detected with (99m)Tc-DMSA scintigraphy before chemotherapy associated nephrotoxicity is observed by laboratory measurements. Our results also imply that, although a tubular agent, renal scintigraphy performed with Tc(99m)-EC is not able to detect subclinical injury or predict the outcome during treatment.
authors.affiliation: Department of Nuclear Medicine, Hacettepe University Medical Faculty, Sihhiye Ankara, 06100 Turkey. mcaglar@hacettepe.edu.tr
authors.forename: M
authors.initials: M
authors.lastname: Caglar
authors.forename: N
authors.initials: N
authors.lastname: Yarís
authors.forename: C
authors.initials: C
authors.lastname: Akyuz
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001692:Biological Transport; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003404:Creatinine / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000493:pharmacokinetics; D007223:Infant; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009369:Neoplasms / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics; D014018:Tissue Distribution; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D001613:beta 2-Microglobulin; C073806:technetium Tc 99m-ethylenedicysteine; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D003404:Creatinine; D003545:Cysteine; D002945:Cisplatin; D007069:Ifosfamide