Specific targeting of activated endothelium in rat adjuvant arthritis with a 99mTc-radiolabeled E-selectin-binding peptide.

Academic Article

Abstract

  • OBJECTIVE: To determine the potential of an E-selectin-binding peptide (ESbp) to specifically bind activated endothelium in rheumatoid arthritis (RA) animal models. METHODS: ESbp (KYDGDITWDQLWDLMK; 2,027 daltons) was labeled with biotin and 99mTc. The affinity of ESbp derivatives for E-selectin was measured by enzyme-linked immunosorbent assay. The binding of biotin-ESbp was compared with that of an anti-E-selectin antibody, by immunohistochemical analyses of human synovial sections and sections from the Mycoplasma pulmonis MRL-lpr/lpr mouse arthritis model. 99mTc-ESbp was sequentially imaged in vivo with a gamma camera in the rat adjuvant-induced arthritis model. RESULTS: E-selectin expression was detected in human RA synovium and mouse arthritic synovium using biotin-ESbp. Both biotin-ESbp and 99mTc-labeled ESbp had high affinity for E-selectin (dissociation constant 2-5 nM). In vivo imaging showed specific binding of 99mTc-ESbp to the rat ankle joint prior to clinical manifestations of inflammation. CONCLUSION: These results demonstrate that activated endothelium can be targeted with 99mTc-ESbp. The specificity of targeting can be used to evaluate up-regulation of E-selectin in RA models, and to follow changes in this up-regulation during treatment trials.
  • Published In

    Keywords

  • Amino Acid Sequence, Animals, Antigens, Bacterial, Arthritis, Experimental, Biotin, Cells, Cultured, Disease Models, Animal, E-Selectin, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Mice, Mice, Inbred MRL lpr, Molecular Sequence Data, Mycoplasma, Osteoarthritis, Peptide Fragments, Protein Binding, Radionuclide Imaging, Rats, Rats, Inbred Lew, Synovial Membrane, Technetium, Umbilical Veins
  • Author List

  • Zinn KR; Chaudhuri TR; Smyth CA; Wu Q; Liu HG; Fleck M; Mountz JD; Mountz JM
  • Start Page

  • 641
  • End Page

  • 649
  • Volume

  • 42
  • Issue

  • 4