title: In vitro evaluation and biodistribution of HER2-targeted liposomes loaded with an (125)I-labelled DNA-intercalator.
abstract: BACKGROUND
  Increasing attention is currently focussed on the issue of finding strategies for the delivery of Auger-electron-emitting radionuclides into tumor cell nuclei.
  
  
  OBJECTIVE
  In this study, we investigated tumor-cell uptake and cell-killing ability in vitro as well as in vivo biodistribution of an (125)I-labelled anthracycline derivative administered by means of HER2-targeted liposomes.
  
  
  METHODS
  Anthracycline derivative Comp1 was radiolabelled with Auger-emitting (125)I and encapsulated in liposomes (DSPC:Chol:DSPE-PEG) using pH-gradient loading. Single-chain fragment F5 was anchored to the liposomes as targeting device for HER2. Uptake and specificity of (125)I-Comp1 delivered via targeting and non-targeting liposomes were analysed in cultured HER2-overexpressing cells. Cell-killing efficacy was evaluated in SKOV3 cells and biodistribution for up to 48 h was studied after intraperitoneal injection in tumor-bearing female BALB/c nu/nu mice.
  
  
  RESULTS
  (125)I-Comp1 was specifically taken up by the cultured cells when administered by means of HER2-targeted liposomes and a clear dose-effect correlation in survival of cells was seen with increasing specific activity. The biodistribution studies revealed that (125)I-Comp1 accumulated in tumors when distributed using HER2-targeted liposomes and that this effect was absent when using non-targeting liposomes.
  
  
  CONCLUSIONS
  The HER2-targeted liposomes possess the properties needed to bring about tumor-specific delivery and therapeutic effect of (125)I-Comp1.
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Fondell
authors.forename: K
authors.initials: K
authors.lastname: Edwards
authors.forename: J
authors.initials: J
authors.lastname: Unga
authors.forename: E
authors.initials: E
authors.lastname: Kullberg
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.forename: L
authors.initials: L
authors.lastname: Gedda
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007364:Intercalating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003630:Daunorubicin; D007364:Intercalating Agents; D007457:Iodine Radioisotopes; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases