Atherosclerosis was induced in ApoE−/− mice by feeding an atherogenic diet. 99mTc-duramycin images were acquired using a small-animal SPECT imager. Six ApoE−/− mice at 20 weeks of age (Group I) were imaged and then sacrificed for ex vivo analyses. Six additional ApoE−/− mice (Group II) were imaged at 20 and 40 weeks of age before sacrifice. Six ApoE wild-type (ApoE+/+) mice (Group III) were imaged at 40 weeks as controls. Five additional ApoE−/− mice (40 weeks of age) (Group IV) were imaged with a 99mTc-labeled inactive peptide, 99mTc-LinDUR, to assess 99mTc-duramycin targeting specificity.
Focal 99mTc-duramycin uptake in the ascending aorta and aortic arch was detected at 20 and 40 weeks in the ApoE−/− mice but not in ApoE+/+ mice. 99mTc-duramycin uptake in the aortic lesions increased 2.2-fold on quantitative imaging in the ApoE−/− mice between 20 and 40 weeks. Autoradiographic and histological data indicated significantly increased 99mTc-duramycin uptake in the ascending aorta and aortic arch associated with advanced plaques. Quantitative autoradiography showed that the ratio of activity in the aortic arch to descending thoracic aorta, which had no plaques or radioactive uptake, was 2.1 times higher at 40 weeks than at 20 weeks (6.62 ± 0.89 vs. 3.18 ± 0.29, P < 0.01). There was barely detectable focal uptake of 99mTc-duramycin in the aortic arch of ApoE+/+ mice. No detectable 99mTc-LinDUR uptake was observed in the aortas of ApoE−/− mice.
PE-targeting properties of 99mTc-duramycin in the atherosclerotic mouse aortas were noninvasively characterized. 99mTc-duramycin is promising in localizing advanced atherosclerotic plaques.