While HDL therapy using the injection of HDL apoA-I mimetics or full-length apoA-I can drastically reduce the atherosclerotic plaque burden, it is still unclear whether such peptides or proteins enter the plaque burden and remove cholesterol from the lesions. We synthesized inducible cholesterol efflux 24-amino acid apoA-I mimetic peptide-type5 (FAMP), which potently removes cholesterol via specific ABCA1. Therefore, the imaging of atherosclerosis using FAMP should represent a functional imaging of HDL. To achieve this end, FAMP was modified with chelator, DOTA and radiolabeled with 68Ga for noninvasive PET in WHHL-MI rabbits with atherosclerotic lesions. 68Ga-DOTA-FAMP, but not the scrambled peptide, was dramatically taken up by atherosclerotic aorta in WHHL-MI rabbits, but not by that in normal rabbits. Oil-red O staining (A) and PPIS imaging (B) were performed in young (a) and old (b) WHHL-MI rabbits, and the plaque area showed a 68Ga reaction. Oil-red O staining in younger WHHL aorta was very similar to the results of PPIS, and old rabbits still trapped more 68Ga-DOTA–FAMP. The radioactivity in stained plaque lesions was greater than that in plaque-poor tissues. As well as PPIS imaging, the radioactivities of aortic tissues by using g-counter were significantly increased in stained plaque lesions.
In summary, a new method for observing atherosclerotic plaque by using PET imaging with a 68Ga-DOTA-FAMP tracer was developed, and FAMP was continuously taken up into the plaque burden, which revealed the mechanism of action of FAMP-cell interactions. According to previous report of the internalization and transcytosis of apoA-I via ABCA1 in macrophages, these observations strongly suggest FAMP is specifically internalized in advanced plaque lesions to promote cholesterol efflux.
