Specific targeting of activated endothelium in rat adjuvant arthritis with a 99mTc-radiolabeled E-selectin–binding peptide
✍ Scribed by Kurt R. Zinn; Tandra R. Chaudhuri; Cheryl A. Smyth; Qi Wu; Hong-Gang Liu; Martin Fleck; John D. Mountz; James M. Mountz
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 310 KB
- Volume
- 42
- Category
- Article
- ISSN
- 0004-3591
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✦ Synopsis
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.