title: Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics.
abstract: OBJECTIVE
  Radiation exposure to the kidney limits therapy with radiometal labelled DOTATOC. This study evaluates the organic anion and cation transport (inhibitors: probenecid and cimetidine/dexamethasone) as well as diuresis (furosemide and mannitol) regarding renal uptake of [(111)In]DOTATOC.
  
  
  METHODS
  One hundred eight male Fisher rats were injected with [(111)In]DOTATOC via the tail vein. Prior to activity injection a total of 84 rats underwent injection with probenecid vs. sodium chloride 0.9% (48 rats), cimetidine vs. dexamethasone vs. sodium chloride 0.9% (18 rats), and furosemide vs. mannitol vs. sodium chloride 0.9% (18 rats). Rats were sacrificed at predetermined time points up to 48 h after activity injection. Kidneys, adrenal glands, pancreas, spleen, blood, liver, and muscle were harvested and injected activity per gram tissue was determined. Autoradiographic images of the kidneys were acquired in a total of 24 rats.
  
  
  RESULTS
  Probenecid led to a reduction in renal uptake by up to 30% while not significantly changing the activity accumulation in the other organs investigated. This reduction was attributable to the renal cortex (ratio cortex/medulla 1.72 vs. 1.99; p = 0.006). Cimetidine and dexamethasone had no effect in any of the organs. Furosemide led to a 44% increase in renal activity accumulation attributable to enhanced renal medullary uptake (ratio cortex/medulla 1.44 versus 1.69; p = 0.006). Mannitol had no effect on renal activity uptake.
  
  
  CONCLUSIONS
  Inhibition of the organic anion transport by probenecid may help reduce renal uptake regarding therapy with radiometal labelled DOTATOC. The enhancing effect of furosemide may be unfavourable for therapy. The results must be confirmed by human studies.
authors: Department of Nuclear Medicine, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, Munich, Germany. a.stahl@lrz.tum.de
authors: A R
authors: AR
authors: Stahl
authors: B
authors: B
authors: Wagner
authors: T
authors: T
authors: Poethko
authors: M
authors: M
authors: Perutka
authors: H J
authors: HJ
authors: Wester
authors: M
authors: M
authors: Essler
authors: U
authors: U
authors: Heemann
authors: M
authors: M
authors: Schwaiger
authors: J
authors: J
authors: Lutz
mesh_terms: D000818:Animals; D004232:Diuretics / Q000008:administration & dosage*; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009928:Organ Specificity; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
chemical_list: C507387:111In-DOTA-TOC; D004232:Diuretics; D027361:Organic Anion Transporters; D019275:Radiopharmaceuticals; D015282:Octreotide
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