MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGEN EXPRESSION IN REJECTING CARDIAC ALLOGRAFTS - DETECTION USING IN-VIVO IMAGING WITH RADIOLABELED MONOCLONAL-ANTIBODY

Background Increased expression of major histocompatibility complex cl ass II (MHC-II) antigen occurs during cardiac allograft rejection. We tested the hypotheses that (1) radiolabeled antibody to MHC-II antigen allows detection of cardiac allograft rejection using nuclear imaging techniques and (2) uptake of radiolabeled antibody to MHC-II antigen correlates with severity of rejection. Methods and Results Thirteen be agles with cervical cardiac allografts were studied for 64+/-23 days b y use of myocardial biopsy and in vivo imaging. Uptake of radiolabeled (I-131 [n=2], I-123 [n=1], or In-111 [n=10]) antibody to MHC-II incre ased over baseline in 7 animals that developed histological evidence o f progressively worsening allograft rejection (group A), from 72.2+/-4 6.1 to 176.8+/-102.0 counts/pixel/mCi (P<.009). In 4 beagles without p rogressively worsening allograft rejection (group B), uptake was uncha nged during follow-up (74.4+/-43.8 and 60.2+/-37.4 counts/pixel/mCi; P =NS). In animals studied with In-111-labeled antibody, uptake increase d from 102.9+/-23.1 at baseline to 233.2+/-82.7 counts/pixel/mCi at fo llow-up in group A animals (P=.036), with no significant change in gro up B (91.1+/-34.9 and 75.9+/-24.9 counts/pixel/mCi; P=NS). Uptake of I n-111-labeled antibody was 107.5+/-35.7, 135.9+/-70.8, and 307.8+/-90. 1 counts/pixel/mCi in biopsy samples showing evidence of mild, moderat e, and severe rejection, respectively (P=.001). Biopsy samples showing mild, moderate, and intense MHC-II expression antibody uptake had upt akes of 92.6+/-36.3, 158.5+/-54.7, and 307.8+/-90.1 counts/pixel/mCi, respectively (P=.00004). Conclusions Radiolabeled monoclonal antibodie s to MHC-II antigen can detect cardiac allograft rejection in this lar ge mammal model of cardiac allograft transplantation, and this techniq ue may have a potential role in the detection of rejection in patients after cardiac transplantation.