title: PEG modification on (111)In-labeled phosphatidyl serine liposomes for imaging of atherosclerotic plaques.
abstract: BACKGROUND
  Previously, we reported a probe for imaging of atherosclerotic plaques: (111)In-labeled liposomes. Liposomes were modified with phosphatidylserine (PS) because macrophages recognize PS and phagocytize apoptotic cells in plaques. PS modification was successful and we could visualize atherosclerotic plaques by single-photon emission computed tomography (SPECT). However, too-rapid blood clearance reduced accumulation of PS-liposomes in plaques in vivo. Therefore, in the present study, PS-liposomes were modified with polyethylene glycol (PEG) to retard the rate of blood clearance.
  
  
  METHODS
  PS-liposomes (size, 100 nm or 200 nm) were PEGylated with PEG2000 or PEG5000 at 1 or 5 mol%, and radiolabeled with (111)In. For the study of uptake in vitro, liposomes were incubated with mouse peritoneal macrophages. Biodistribution studies in vivo were carried out in ddY mice. En face autoradiograms were obtained with apoE(-/-) mice upon intravenous injection of (111)In-liposomes.
  
  
  RESULTS
  Uptake was decreased significantly at 5 mol% PEGylation in 100-nm PS-liposomes (*P<0.05 vs. 0 mol%). All the PEGylated liposomes tested showed significantly lower uptake than the non-PEGylated control in 200-nm liposomes. In vivo results showed slower blood clearance in PEGylated liposomes. Autoradiograms in apoE(-/-) mice were well matched with Oil Red O staining. Additionally, 200-nm PS-liposomes modified with 5%PEG2000 ([(111)In]5%PEG2000PS200) showed the highest uptake to the region in vivo.
  
  
  CONCLUSIONS
  As expected, PEGylation retarded the rate of blood clearance. In addition, it affected liposome uptake by macrophages in vitro. These results suggest that the balance between the rate of blood clearance and macrophage recognition is important, and [(111)In]5%PEG2000PS200 showed the best results in our investigation.
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan. Electronic address: mogawa@hama-med.ac.jp.
authors.forename: Mikako
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Uchino
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kawai
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kosugi
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Magata
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001692:Biological Transport; D007205:Indium Radioisotopes; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010718:Phosphatidylserines / Q000737:chemistry*; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001057:Apolipoproteins E; D007205:Indium Radioisotopes; D008081:Liposomes; D010718:Phosphatidylserines; D011092:Polyethylene Glycols
keywords: Atherosclerosis; Liposome; Macrophage; PEG