title: Inhibition of renal uptake of indium-111-DTPA-octreotide in vivo.
abstract: Indium-111-DTPA-octreotide has been successfully used for imaging of somatostatin receptor-positive lesions. However, significant renal uptake of 111In-DTPA-octreotide exists, reducing the scintigraphic sensitivity for detection of small tumors in the perirenal region and the possibilities for radiotherapy. The aim of the present study was to determine whether renal uptake of 111In-DTPA-octreotide could be reduced in vivo in rats.
  
  
  METHODS
  Male Wistar rats (200-250 g) were placed in metabolic cages and injected with 111In-DTPA-octreotide (0.2 MBq and 0.5 microgram octreotide), in the presence or absence of re-uptake blockers. At time t = 20 hr after injection, rats were sacrificed and organs were isolated and counted for radioactivity.
  
  
  RESULTS
  Adding NH4Cl or NaHCO3 to the food, resulting in the production of more acid or alkaline urine respectively, resulted in less radioactivity in the kidneys 20 hr after injection compared to controls. Lysine in a single dose of 400 mg/kg resulted in an inhibition of kidney uptake of 40%. When lysine was injected 30 min before 111In-DTPA-octreotide, the inhibition was 25%. Arginine had less effect on tubular uptake of 111In-DTPA-octreotide than lysine (20% inhibition). Sodium maleate inhibited kidney uptake of 111In-DTPA-octreotide most successfully. Acetazolamide (100 mg/kg), succinylacetone (100 mg/kg), cystine dimethylester (340 mg/kg) and increase in urinary flow did not influence 111In-DTPA-octreotide retention in the kidneys.
  
  
  CONCLUSIONS
  It appeared possible to reduce re-uptake of 111In-DTPA-octreotide in the rat kidney in vivo. The most pronounced effects were seen after administration of sodium maleate or lysine but, because of the described toxic effects of maleate, we will study further only the effects of lysine in a clinical setting.
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical University, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: E J
authors.initials: EJ
authors.lastname: Rolleman
authors.forename: B F
authors.initials: BF
authors.lastname: Bernard
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.forename: W H
authors.initials: WH
authors.lastname: Bakker
authors.forename: W A
authors.initials: WA
authors.lastname: Breeman
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003553:Cystine / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006537:Heptanoates / Q000494:pharmacology; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000494:pharmacology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D004791:Enzyme Inhibitors; D006537:Heptanoates; D008298:Maleates; C071632:SDZ 215-811; D003553:Cystine; C020804:succinylacetone; D004369:Pentetic Acid; C030272:maleic acid; D001120:Arginine; D008239:Lysine; D000086:Acetazolamide; D015282:Octreotide; C034582:cystine dimethyl ester