Radiolabeled MDA2, an oxidation-specific, monoclonal antibody, identifies native atherosclerotic lesions in vivo

Abstract

Radiolabeled MDA2 shows excellent in vivo uptake and specificity for atherosclerotic lesions containing abundant oxidation-specific epitopes. The in vivo imaging studies suggest that noninvasive imaging of oxidation-rich atherosclerotic lesions with radiolabeled MDA2 may be feasible in human beings with optimization of the imaging methods.

In Vivo Uptake of Radiolabeled MDA2, an Oxidation-Specific Monoclonal Antibody, Provides an Accurate Measure of Atherosclerotic Lesions Rich in Oxidized LDL and Is Highly Sensitive to Their Regression

“…This is in agreement with our previous observation that autoradiographs of WHHL rabbit aortas accurately reflect Sudan-positive lesions. 19 In contrast, in the chow ( Figure 5B) and chowϩvitamin Eϩvitamin C groups, some areas containing large Sudanpositive lesions did not show MDA2 uptake by autoradiography (arrow in Figure 5B), implying that these lesions contained fewer oxidation-specific epitopes. Note that to demonstrate differences in oxidation-specific epitopes detected by autoradiography, we deliberately selected arteries with a similar extent of atherosclerosis for Figure 5.…”

“…We previously demonstrated by ELISA that radiolabeling does not significantly affect antigen binding of MDA2. 19 …”

“…14,16,18 We have previously shown that 125 I-labeled MDA2 ( 125 I-MDA2) can be used to detect atherosclerotic lesions in rabbit aortas by autoradiography and that 99m Tc-labeled MDA2 can be used to noninvasively image atherosclerotic lesions in live rabbits. 19 However, OxLDL content of lesions varies, depending on their stage, and some of the labeled antibody detected in atherosclerotic lesions undoubtedly reflects increased permeability to macromolecules in general rather than specific binding to OxLDL. Therefore, a careful assessment of how much of the arterial MDA2 uptake represents specific binding to oxidation-specific epitopes and a comparison of MDA2 uptake with traditional measures of plaque burden are necessary.…”

Percutaneous Coronary Intervention Results in Acute Increases in Oxidized Phospholipids and Lipoprotein(a)

“…One possibility is that both OxPL and Lp(a) are derived from disrupted plaque contents, inasmuch as both have been previously documented to be enriched in atherosclerotic lesions in vivo. [1][2][3]5,9,10,20 In fact, recent work in animal models demonstrates that OxLDL can be imaged noninvasively with radiolabeled oxidation-specific antibodies. 2,5 Sev- …”

“…[1][2][3][4] In animals, OxLDL within plaques is preferentially depleted in response to regression/antioxidant diets. [5][6][7] In humans, plaque specimens from carotid and coronary arteries are significantly enriched in OxLDL 1,3 and become depleted in OxLDL after treatment with statins.…”