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

The oligopeptide fragment of apolipoprotein B, SP-4, has demonstrated pronounced uptake in the healing edges of balloon-injured rabbit aorti c endothelium. To assess I-123-labeled SP-4 for identification of athe rosclerotic plaques by gamma camera imaging, 14 Watanabe heritable hyp erlipidemic (WHHL) and 5 normal rabbits were imaged 5 minutes and 12 a nd 24 hours after intravenous injection of I-123-SP-4. In addition, tw o WHHL and two normal rabbits were injected with I-125-SP-4 for autora diography. 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 rabb its were reimaged 4 and 8 weeks later with I-123-NaI and I-123-SP-2 (a n 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 rabbi t aortas did not exhibit plaques on photographs or film blackening on autoradiograms. Thus, in an animal model closely simulating human athe rosclerotic disease, SP-4 localizes specifically in aortic atheroscler otic lesions.