RAT ADJUVANT ARTHRITIS - IMAGING WITH TECHNETIUM-99M-ANTI-CD4 FAB' FRAGMENTS

The abundance of CD4 molecules on inflammatory cells in the synovial m embrane renders anti-CD4 monoclonal antibodies (MAbs) or their fragmen ts very promising for specific imaging of arthritic joints. Methods: J oint uptake and body distribution of a Tc-99m-labeled Fab', derived fr om the anti-rat CD4 MAb W3/25 (IgG(1)), were investigated following in travenous injection in normal and adjuvant arthritic rats. An isotype- matched Fab' (antihuman nonspecific crossreacting antigen-90) was used as control. Results: A 14-hr sequential pinhole scan of the ankle joi nts revealed that both the anti-CD4 and the control Fab' accumulated t o a higher degree in arthritic than in normal ankle joints; however, a ccumulation of the anti-CD4 Fab' in arthritic joints exceeded that of the control Fab' (similar to 1.6 fold). Preferential joint accumulatio n of anti-CD4 Fab' was confirmed by whole-body scans at 14 hr and by d irect well counter measurements of tissue samples at 16 hr following i njection. Unlike the control Fab', the anti-CD4 Fab' preferentially ac cumulated in the liver and lymph nodes, organs rich in CD4-positive ce lls, as observed by direct tissue measurements. Conclusion: Despite it s monovalency, the anti-CD4 Fab' retains the in vivo selectivity for C D4-positive cell-rich tissues, previously reported for the complete an ti-CD4 MAb, and improves imaging of inflamed joints in experimental ad juvant arthritis.