title: Uptake of [111In-DTPA0]octreotide in the rat kidney is inhibited by colchicine and not by fructose.
abstract: The high renal uptake of radiolabeled somatostatin analogs is dose limiting. Lowering this uptake permits higher radioactivity doses and, thus, tumor doses to be administered. We tested the effects of the microtubule drug colchicine on renal uptake of [(111)In-DTPA(0)]octreotide. Also, the effects of fructose were tested.
  
  
  METHODS
  Organ radioactivity 24 h after injection of [(111)In-DTPA(0)]octreotide was determined in rats.
  
  
  RESULTS
  Coinjection of 1 mg of colchicine per kilogram did not influence renal uptake of [(111)In-DTPA(0)]octreotide, whereas this dose administered 5 h before [(111)In-DTPA(0)]octreotide resulted in significant renal uptake reduction (63%). D-Lysine plus colchicine reduced the uptake by 76% (P < 0.01 vs. D-lysine alone). Liver and blood radioactivity levels were significantly elevated by colchicine. Fructose did not affect the biodistribution of [(111)In-DTPA(0)]octreotide.
  
  
  CONCLUSIONS
  Renal uptake of [(111)In-DTPA(0)]octreotide is dependent on microtubule function in rats. The addition of colchicine to amino acid protocols may permit administration of higher doses, improving the therapeutic window of peptide receptor radionuclide therapy.
authors.affiliation: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. e.rolleman@erasmusmc.nl
authors.forename: Edgar J
authors.initials: EJ
authors.lastname: Rolleman
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Arthur
authors.initials: A
authors.lastname: Van Gameren
authors.forename: Bert F
authors.initials: BF
authors.lastname: Bernard
authors.forename: Marion
authors.initials: M
authors.lastname: De Jong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology*; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D015282:Octreotide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D009928:Organ Specificity; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D011866:Radioisotope Renography; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; C071632:SDZ 215-811; D005632:Fructose; D004369:Pentetic Acid; D000255:Adenosine Triphosphate; D015282:Octreotide; D003078:Colchicine