title: Intravenous technetium-99m labelled PEG-liposomes in horses: a safety and biodistribution study.
abstract: BACKGROUND
  Liposomes are phospholipid nanoparticles that extravasate at sites of increased vascular permeability. They have potential in equine medicine for targeted drug delivery and diagnostic imaging of infectious, inflammatory and neoplastic lesions.
  
  
  OBJECTIVE
  This study evaluates the safety and biodistribution of i.v. polyethyleneglycol(PEG) liposomes in normal horses.
  
  
  METHODS
  PEG-liposomes were prepared by the film hydration method and labelled using (99m) Tc-hexamethyl-propylene-amine-oxime. A single dose of 0.24 µmol/kg bwt (99m) Tc-PEG-liposomes and 2.4 µmol/kg bwt unlabelled PEG-liposomes was administered to 10 conscious horses via i.v. infusion at a rate of 6 µmol/min for the first 15 min and 60 µmol/min thereafter. Clinical parameters, haematology, plasma biochemistry and serum complement activity were monitored serially. Scintigraphic imaging was performed at 1, 12 and 21 h post infusion (PI). Six horses were subjected to euthanasia at 24 h PI. The percentage injected dose per kilogram of tissue was calculated for multiple organs. Results were analysed using repeated measures ANOVA.
  
  
  RESULTS
  Horses did not demonstrate adverse reactions during or after liposome infusion. There was a significant elevation in heart rate and respiratory rate at 20 and 25 min PI. No significant complement consumption was detected, although a trend for decreased total haemolytic complement values at 20 min PI was present. Scintigraphic studies revealed a prolonged vascular phase that lasted to 21 h PI, with a reproducible pattern of organ distribution. Biodistribution studies revealed the highest concentrations of radiopharmaceutical within the lung, kidney, liver and spleen.
  
  
  CONCLUSIONS
  Intravenous liposome administration appears to be safe in horses. When administered in combination with PEG-liposomes, (99m) Tc-PEG-liposomes have long circulating characteristics and a reproducible pattern of organ distribution in horses.
  
  
  CONCLUSIONS
  Radiolabelled liposomes may be useful for detecting infection, inflammation and neoplasia in the horse. Liposomes have significant potential for targeted drug delivery in the horse. This study establishes the scintigraphic findings and tissue distribution of 99mTc-PEG-liposomes after i.v. administration in healthy horses.
authors.affiliation: Department of Clinical Studies New Bolton Center, Kennett Square, University of Pennsylvania, School of Veterinary Medicine, PA, USA. claire.underwood@uqconnect.edu.au
authors.forename: C
authors.initials: C
authors.lastname: Underwood
authors.forename: A W
authors.initials: AW
authors.lastname: van Eps
authors.forename: M W
authors.initials: MW
authors.lastname: Ross
authors.forename: P
authors.initials: P
authors.lastname: Laverman
authors.forename: L
authors.initials: L
authors.lastname: van Bloois
authors.forename: G
authors.initials: G
authors.lastname: Storm
authors.forename: T P
authors.initials: TP
authors.lastname: Schaer
mesh_terms: D000818:Animals; D005260:Female; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D019690:Technetium Tc 99m Exametazime / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime; D011092:Polyethylene Glycols