Rat adjuvant arthritis: imaging with technetium-99m-anti-CD4 Fab' fragments.
The abundance of CD4 molecules on inflammatory cells in the synovial membrane renders anti-CD4 monoclonal antibodies (MAbs) or their fragments very promising for specific imaging of arthritic joints.


METHODS
Joint uptake and body distribution of a 99mTc-labeled Fab', derived from the anti-rat CD4 MAb W3/25 (IgG1), were investigated following intravenous injection in normal and adjuvant arthritic rats. An isotype-matched Fab' (anti-human nonspecific crossreacting antigen-90) was used as control.


RESULTS
A 14-hr sequential pinhole scan of the ankle joints revealed that both the anti-CD4 and the control Fab' accumulated to a higher degree in arthritic than in normal ankle joints; however, accumulation of the anti-CD4 Fab' in arthritic joints exceeded that of the control Fab' (approximate to 1.6 fold). Preferential joint accumulation of anti-CD4 Fab' was confirmed by whole-body scans at 14 hr and by direct well counter measurements of tissue samples at 16 hr following injection. Unlike the control Fab', the anti-CD4 Fab' preferentially accumulated in the liver and lymph nodes, organs rich in CD4-positive cells, as observed by direct tissue measurements.


CONCLUSIONS
Despite its monovalency, the anti-CD4 Fab' retains the in vivo selectivity for CD4-positive cell-rich tissues, previously reported for the complete anti-CD4 MAb, and improves imaging of inflamed joints in experimental adjuvant arthritis.
Max-Planck-Society, Department of Medicine III, University of Erlangen-Nuremberg, Germany.
R W
RW
Kinne
W
W
Becker
T
T
Koscheck
J
J
Kuhlmann
R M
RM
Sharkey
T
T
Behr
E
E
Palombo-Kinne
D M
DM
Goldenberg
F
F
Wolf
F
F
Emmrich
D000818:Animals; D000843:Ankle Joint / Q000000981:diagnostic imaging; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging*; D015704:CD4 Antigens / Q000276:immunology*; D005260:Female; D007140:Immunoglobulin Fab Fragments; D016719:Radioimmunodetection / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D013667:Technetium; D014018:Tissue Distribution
D015704:CD4 Antigens; D007140:Immunoglobulin Fab Fragments; D013667:Technetium