Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics

Eur J Nucl Med Mol Imaging. 2007 Dec;34(12):2129-34. doi: 10.1007/s00259-007-0519-x. Epub 2007 Aug 11.


Aim: 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Diuretics / administration & dosage*
  • Kidney / diagnostic imaging
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Metabolic Clearance Rate / drug effects
  • Octreotide / analogs & derivatives*
  • Octreotide / pharmacokinetics
  • Organ Specificity
  • Organic Anion Transporters / antagonists & inhibitors*
  • Organic Anion Transporters / metabolism*
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Inbred F344
  • Tissue Distribution


  • 111In-DOTA-TOC
  • Diuretics
  • Organic Anion Transporters
  • Radiopharmaceuticals
  • Octreotide