title: Glomerular filtration rate and the kinetics of 123I-metaiodobenzylguanidine.
abstract: We have recently reported evidence that the calcium antagonist nifedipine can improve the tumour retention of 131I-metaidobenzylguanidine (131I-MIBG) in patients with malignant phaeochromocytoma. During studies of the pharmacological modification of tumour MIBG kinetics, it is important to distinguish clearly between a direct effect on MIBG cellular retention by a pharmaceutical, and secondary effects due, for example, to a change in glomerular filtration rate (GFR). In order to provide the fundamental kinetic data required for the numerical modelling of the effect of nifedipine on tumour MIBG kinetics, we have investigated the influence of GFR on MIBG plasma and renal kinetics. The 123I-MIBG plasma curve and MIBG renal plasma clearance rate were studied in ten patients, ranging from subjects without biochemical or scintigraphic evidence of phaeochromocytoma to individuals with widely disseminated metastatic disease. GFR was measured using the 99mTc-DTPA plasma clearance method. In four cases, the studies were repeated with the patients taking oral nifedipine. Statistically significant correlations were found between GFR and the MIBG plasma concentration. MIBG renal plasma clearance rate and the early (0 to 5 min) renal excretion of MIBG. The data permit the evaluation of the plasma integral during the first few min following bolus injection, a quantity important in the numerical modelling of tumour kinetics. GFR was found to have a major influence on whole-body MIBG kinetics, but there was also evidence of the effect of the metastatic tumour burden.
authors.affiliation: Department of Nuclear Medicine, Guy's Hospital, London, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Blake
authors.forename: V J
authors.initials: VJ
authors.lastname: Lewington
authors.forename: M A
authors.initials: MA
authors.lastname: Zivanovic
authors.forename: D M
authors.initials: DM
authors.lastname: Ackery
mesh_terms: D019797:3-Iodobenzylguanidine; D000328:Adult; D003131:Combined Modality Therapy; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D007462:Iodobenzenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009543:Nifedipine / Q000627:therapeutic use; D010673:Pheochromocytoma / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*
chemical_list: D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D019797:3-Iodobenzylguanidine; D009543:Nifedipine