803-4 Very Early Noninvasive Visualization of Experimental Atherosclerosis with Chimeric Antibody Z2D3 Radiolabeled with In-111 via Negatively-Charged Chelating Polymer, or Tc-99m via Glucarate Transchelation

We had reported the feasibility of noninvasive imaging of experimental atherosclerotic lesions with Indium-ll1-labeled mouselhuman chimeric Z2D3 F(ab’)2 specific for proliferating smooth muscle cells in human atheroma. Lesions were visualized by 48 H. To reduce the delay between visualization and antibody administration, (i), Z2D3 F(ab’)2 was labeled with In-111 via negatively-charged chelating polymers (specific activity 500–1300 MBq/mg) and compared to the conventional In-111 labeled counterpart (specific activity 32–48MBq/mg); and (ii), Z2D3 Fab’ was labeled with Tc-99m via a weak transchelator, glucaric acid.In vivo targeting was evaluated in 16 rabbits with atherosclerotic lesions induced by infradiaphragmatic balloon deendothelialization of the abdominal aorta followed by hyperlipidemic diet for 12 weeks. Four rabbits received 24 MBq (50μg) of In-111-< Charge modified Z203 F(ab’)2 Two rabbits received 130 MBq (100μg) of the kit formulation of this preparation. Six rabbits received 24 MBq (500–750μg) of conventional Z2D3 F(ab’)2. The remaining 4 animals received Tc-99m Z203 Fab’ (500-600 Mbq/375μg). Gamma imaging revealed unequivocal tracer uptake in the abdominal atherosclerotic lesions at 24 H in all 4 animals injected with modified Z2D3. In 2 rabbits with higher specific radioactivity, the lesions could be visualized at 3 H. The blood pool activity in rabbits injected with the conventional Z2D3 did not permit definitive visualization of the lesions before 48 H. Blood clearance was significantly faster with modified Z2D3 (0.10±0.008, Mean %ID/g±SEM), as compared to the conventional Z2D3 (0.29±0.04; P<0.01). Uptake of modified Z2D3 preparations in atherosclerotic lesions at 24 H (0.08±0.01) was similar to the conventional Z2D3 at 48 H(0.08±0.02; P=NS). Tc-Fab’ localization was visualizable at 12 H after administration of antibody. The Tc-Fab’ uptake in the atherosclerotic lesion was significantly higher in the lesion (0.022±0.004) compared to the normal (0.013±0.002; p=0.04) aorta. This study demon strated the feasibility of very early noninvasive visualization of atherosclerotic lesions with antibody-based scintigraphy