EXTERNAL IMAGING OF ATHEROSCLEROSIS IN RABBITS USING AN I-123 LABELED SYNTHETIC PEPTIDE FRAGMENT

The oligopeptide fragment of apolipoprotein B, SP-4, has demonstrated pronounced uptake in the healing edges of balloon-injured rabbit aortic endothelium. To assess I-123-labeled SP-4 for identification of atherosclerotic plaques by gamma camera imaging, 14 Watanabe heritable hyperlipidemic (WHHL) and 5 normal rabbits were imaged 5 minutes and 12 and 24 hours after intravenous injection of I-123-SP-4. In addition, two WHHL and two normal rabbits were injected with I-125-SP-4 for autoradiography. Twelve of the 14 WHHL, but none of the normal, rabbits had visually apparent focal radioiodine accumulation in the region of the aorta. Focus-to-lung and focus-to-heart count ratios were 2.4 +/- 1.3 and 1.0 +/- 0.4, respectively. Five of the visually positive WHHL rabbits were reimaged 4 and 8 weeks later with I-123-NaI and I-123-SP-2 (an apo E peptide), respectively, as negative controls. Perceptible, but faint, aortic localization of I-123-NaI and of I-123-SP-2 was seen in only one animal each. The distributions of atherosclerotic lesions on photographs of the opened WHHL aortas and of film blackening on I-125-SP-4 autoradiograms were identical. In contrast, the two normal rabbit aortas did not exhibit plaques on photographs or film blackening on autoradiograms. Thus, in an animal model closely simulating human atherosclerotic disease, SP-4 localizes specifically in aortic atherosclerotic lesions.