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

Academic Article


  • 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

    Pubmed Id

  • 23892378
  • 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