title: Reduction of renal uptake of radiolabeled octreotate by amifostine coadministration.
abstract: Megalin-mediated renal retention of radiolabeled somatostatin analogs may lead to nephrotoxicity during peptide receptor radionuclide therapy (PRRT). The cytoprotective agent amifostine protected rats from long-term nephrotoxicity after PRRT with (177)Lu-DOTA,Tyr(3)-octreotate. This study describes the direct effect of amifostine on kidney and tumor uptake of (111)In-DOTA,Tyr(3)-octreotate.
  
  
  METHODS
  In vivo biodistribution studies were performed using CA20948 tumor-bearing rats, with or without amifostine coadministration, via several routes. In vitro uptake was studied in somatostatin receptor-expressing CA20948 and megalin or cubilin receptor-expressing BN-16 cells, in the absence or presence of amifostine or its active metabolite WR-1065.
  
  
  RESULTS
  Coadministration of amifostine decreased renal uptake of radiolabeled octreotate in vivo, whereas tumor uptake was not affected. In agreement, amifostine and WR-1065 coincubation reduced uptake in BN-16 but not in CA20948 cells.
  
  
  CONCLUSIONS
  Amifostine may provide renal protection during PRRT using somatostatin analogs, both by mitigation of radiation damage and the currently observed reduction of absorbed kidney radiation dose.
authors.affiliation: Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. m.melis@erasmusmc.nl
authors.forename: Marleen
authors.initials: M
authors.lastname: Melis
authors.forename: Roelf
authors.initials: R
authors.lastname: Valkema
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: Marion
authors.initials: M
authors.lastname: de Jong
mesh_terms: D004999:Amifostine / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic; D007553:Isotope Labeling; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: C572954:111indium-DOTA, Tyr(3)-octreotate; D056831:Coordination Complexes; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; D017481:Receptors, Somatostatin; D004999:Amifostine; D015282:Octreotide