Radioiodinated peptide probe for selective detection of oxidized low density lipoprotein in atherosclerotic plaques

IntroductionDespite the significant effort in developing radioprobes for atherosclerosis, few have low molecular weight. Oxidized LDL (OxLDL), a highly proinflammatory and proatherogenic factor that is abundant in atherosclerotic plaques, plays a pivotal role in plaque destabilization, which makes OxLDL a relevant probe target. We developed a radioiodinated short peptide, AHP7, as a low molecular weight probe for specific OxLDL imaging and evaluated its utility using myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI).Methods[125I]AHP7 was designed and synthesized based on the sequence of Asp-hemolysin, an OxLDL binding protein extracted from Aspergillus fumigatus. In vitro binding studies with OxLDL having varying degrees of oxidation were performed. Radioactivity accumulation in the aorta was measured 30 min post-administration in rabbits. Autoradiography and histological studies were performed using serial aorta sections. A radioiodinated scrambled peptide ([125I]AHP scramble) was used as a negative control.Results[125I]AHP7 bound to OxLDL in proportion to the degree of oxidation (R = 0.91, P < 0.0001) and was inhibited by unlabeled AHP7 in a concentration-dependent manner. The aorta accumulation level and aorta/blood and aorta/muscle ratios of [125I]AHP7 in WHHLMI were 2.8-, 1.3- and 1.8-fold higher, respectively, than those in control rabbits (P < 0.001). Co-administration of AHP7 significantly reduced [125I]AHP7 radioactivity in aorta sections (P < 0.0001). Regional radioactivity levels in the aorta sections showed nonuniformity but similarity to the immunohistochemical OxLDL density.ConclusionsThe potential of radioiodinated AHP7 for selectively imaging OxLDL was demonstrated both in vitro and in vivo.