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


CONCLUSIONS
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.
Zinn
K R
KR
University of Alabama at Birmingham, 35294-0012, USA.
Chaudhuri
T R
TR
Smyth
C A
CA
Wu
Q
Q
Liu
H G
HG
Fleck
M
M
Mountz
J D
JD
Mountz
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism; D001710:Biotin; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019040:E-Selectin / Q000032:analysis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D009174:Mycoplasma / Q000276:immunology; D010003:Osteoarthritis / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D011877:Radionuclide Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D013667:Technetium; D014471:Umbilical Veins / Q000166:cytology
D000942:Antigens, Bacterial; D019040:E-Selectin; D010446:Peptide Fragments; D001710:Biotin; D013667:Technetium