title: 99mTc-technetium labeling of antiarthritic peptides to evaluate homing and biodistribution at inflamed joints.
abstract: OBJECTIVE
  The aim of this study was to investigate the biodistribution and localization of an anti-inflammatory nonapeptide coupled to synovial targeting peptide (HAP-1) in rat adjuvant-induced arthritis.
  
  
  METHODS
  N(ε)-functionalized histidine derivative was coupled to the N-terminus of core peptide (CP) and HAP-1 to allow coupling of (99m)Tc-tricarbonyl linker (Isolink). Synovial homing peptide HAP-1 was linked to CP through a peptide bond prior to labeling with (99m)Tc. Peptides were purified by high-performance liquid chromatography, characterized by mass spectrometry, radiolabeled and injected into normal and arthritic rats to determine biodistribution and localization.
  
  
  RESULTS
  Gamma scintigraphy imaging showed that the biodistribution of all (99m)Tc-labeled peptides were higher in the arthritic joints compared with the normal nonarthritic joints, at all three time points (10 min, 1 h, 3 h postinjection) and attributed to increased blood flow to inflammatory sites. HAP-1 and CP-HAP-1 showed a greater uptake and localization to arthritic joints compared with controls. There was no difference in the physiological biodistribution of these agents in the heart, kidneys and the bladder.
  
  
  CONCLUSIONS
  This study highlights the versatility of using the His derivative linker for (99m)Tc tagging of a variety of peptides. It also demonstrates greater peptide localization and thereby bioavailability of therapeutic peptides to inflamed joints following specific conjugation to homing peptides. The ability to localize peptide/drugs to inflamed synovium has important therapeutic implications.
authors: Department of Rheumatology, Westmead Hospital, Sydney 2145, Australia.
authors: Marina
authors: M
authors: Ali
authors: Anne
authors: A
authors: Vanniasinghe
authors: Vijay
authors: V
authors: Kumar
authors: Robert
authors: R
authors: Barnett
authors: Roger
authors: R
authors: Alberto
authors: Nicholas
authors: N
authors: Manolios
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D001168:Arthritis / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000378:metabolism; D007553:Isotope Labeling; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D013667:Technetium / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D009842:Oligopeptides; D013667:Technetium