title: Technetium-99m labelled liposomes to image experimental arthritis.
abstract: OBJECTIVE
  Liposomes sterically stabilised with polyethylene glycol (PEG) labelled with technetium-99m were tested for their ability to image adjuvant arthritis in a rat model.
  
  
  METHODS
  Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with 99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
  
  
  RESULTS
  The pharmacokinetics of the radiopharmaceuticals differed considerably (halflife in the blood: PEG-liposomes (18 hours) > 99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/ g) > 99mTc-IgG (0.35% ID/g) > non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
  
  
  CONCLUSIONS
  This study shows that 99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.
authors.affiliation: Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: W J
authors.initials: WJ
authors.lastname: Oyen
authors.forename: G
authors.initials: G
authors.lastname: Storm
authors.forename: M L
authors.initials: ML
authors.lastname: Corvo
authors.forename: L
authors.initials: L
authors.lastname: van Bloois
authors.forename: J W
authors.initials: JW
authors.lastname: van der Meer
authors.forename: F H
authors.initials: FH
authors.lastname: Corstens
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000000981:diagnostic imaging / Q000378:metabolism; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010091:Oximes / Q000493:pharmacokinetics; D011092:Polyethylene Glycols; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000378:metabolism / Q000493:pharmacokinetics; D019690:Technetium Tc 99m Exametazime; D014018:Tissue Distribution
chemical_list: D007136:Immunoglobulins; D008081:Liposomes; D015609:Organotechnetium Compounds; D010091:Oximes; C065376:technetium Tc 99m immunoglobulin; D019690:Technetium Tc 99m Exametazime; D011092:Polyethylene Glycols; D013667:Technetium