Evaluation of indium-111-polyclonal immunoglobulin G to quantitate atherosclerosis in Watanabe heritable hyperlipidemic rabbits with scintigraphy: effect of age and treatment with antioxidants or ethinylestradiol.

Scintigraphic detection of atherosclerotic lesions using 111In-polyclonal IgG was studied. In Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for hypercholesterolemia with spontaneous atherosclerosis, aged WHHL rabbits incorporated more 111In-IgG into atherosclerotic lesions than young WHHL or control NZW rabbits. This result is in agreement with histological analysis. However, due to the low ratio of lesion-incorporated radioactivity to circulating radioactivity, in vivo gamma imaging of atherosclerosis with 111In-IgG scintigraphy was unsuccessful. Interventional agents, Probucol or vitamin E, used for 28 days to reduce the amount of autoantibodies produced against biological modified low-density lipoproteins did not produce differences in 111In-IgG incorporation into the aorta ex vivo. Ethinylestradiol, used for 28 days, exhibited similar incorporation with decreased serum cholesterol by 45%. Although atherosclerosis histology and lesion surfaces of WHHL rabbits are similar to those in adult humans, it is obvious that noninvasive gamma imaging with polyclonal 111In scintigraphy is not reliable for serial evaluation of the extent of atherosclerosis. Our results emphasize the need to develop pharmaceuticals to image atherosclerosis.