Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies.
OBJECTIVE
The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA).


METHODS
AA rat peritoneal macrophages or lymph node l-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA.


RESULTS
In vitro release of 99mTc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joint scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints.


CONCLUSIONS
While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99mTc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible.
Experimental Rheumatology Unit, Friedrich Schiller University of Jena. Raimund.W.Kinne@rz.uni-jena.de
R W
RW
Kinne
A
A
Wolski
E
E
Palombo-Kinne
F
F
Wolf
F
F
Emmrich
W
W
Becker
D000818:Animals; D000911:Antibodies, Monoclonal; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging*; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D007249:Inflammation / Q000000981:diagnostic imaging; D007592:Joint Diseases / Q000000981:diagnostic imaging*; D008264:Macrophages / Q000378:metabolism; D016719:Radioimmunodetection / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D013667:Technetium