title: SPECT imaging of peripheral amyloid in mice by targeting hyper-sulfated heparan sulfate proteoglycans with specific scFv antibodies.
abstract: BACKGROUND
  Amyloid deposits are associated with a broad spectrum of disorders including monoclonal gammopathies, chronic inflammation, and Alzheimer's disease. In all cases, the amyloid pathology contains, in addition to protein fibrils, a plethora of associated molecules, including high concentrations of heparan sulfate proteoglycans (HSPGs).
  
  
  METHODS
  We have evaluated radioiodinated scFvs that bind HS for their ability to image amyloid deposits in vivo. scFv's with different binding characteristics were isolated by phage display using HS extracted from bovine kidney or mouse and human skeletal muscle glycosaminoglycans (GAGs). Following purification and radioiodination, the biodistribution of (125)I-scFv's was assessed in mice with inflammation-associated AA amyloidosis or in amyloid-free mice by using SPECT imaging, biodistribution measurements and tissue autoradiography.
  
  
  RESULTS
  Four different scFv's all showed binding in vivo to amyloid in the spleen, liver and kidney of diseased mice; however, three of the scFv's also bound to sites within these organs in disease free mice. One scFv specific for hypersulfated HSPGs preferentially bound amyloid and did not accumulate in healthy tissues.
  
  
  CONCLUSIONS
  These data indicate that HS expressed in amyloid deposits has unique qualities that can be distinguished from HS in normal tissues. A scFv specific for rare hypersulfated HS was used to selectively image AA amyloid in mice with minimal retention in normal tissue.
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, TN 37922, USA. jwall@utmck.edu
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wall
authors.forename: Tina
authors.initials: T
authors.lastname: Richey
authors.forename: Alan
authors.initials: A
authors.lastname: Stuckey
authors.forename: Robert
authors.initials: R
authors.lastname: Donnell
authors.forename: Arie
authors.initials: A
authors.lastname: Oosterhof
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Smits
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel
mesh_terms: D000686:Amyloidosis / Q000000981:diagnostic imaging*; D000818:Animals; D001345:Autoradiography; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D007674:Kidney Diseases / Q000000981:diagnostic imaging*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008107:Liver Diseases / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D057127:Single-Chain Antibodies / Q000493:pharmacokinetics*; D013154:Spleen / Q000000981:diagnostic imaging / Q000378:metabolism; D013158:Splenic Diseases / Q000000981:diagnostic imaging*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed
chemical_list: D019812:Heparan Sulfate Proteoglycans; D007457:Iodine Radioisotopes; D057127:Single-Chain Antibodies