Reduced in vivo aortic uptake of radiolabeled oxidation-specific antibodies reflects changes in plaque composition consistent with plaque stabilization.
OBJECTIVE
Labeled oxidation-specific antibodies (Ox-AB) detect, quantify, and noninvasively image lipid-rich atherosclerotic lesions. However, it is unknown whether Ox-AB detect plaque stabilization.


RESULTS
The aortic uptake of intravenously injected 125I-MDA2 (Ox-AB to malondialdehyde [MDA]-low-density lipoprotein [LDL]) was quantitated in: (1) LDL receptor-/- mice with established atherosclerosis continued on Western diet (Progression) or switched to chow (Regression) or chow+vitamins E and C (Regression-VIT) for 6 months; and (2) Watanabe rabbits (3- to 57-months old) with naturally evolved atherosclerotic lesions. In mice, the Progression group had more extensive atherosclerosis, higher 125I-MDA2 uptake, high concordance of Sudan (lipid)-staining and 125I-MDA2 uptake, and stronger oxidized LDL (OxLDL) and macrophage immunostaining than both Regression groups. In contrast, the Regression groups showed Sudan-positive lesions with focally diminished 125I-MDA2 uptake, which coincided with reduced OxLDL and macrophages but more smooth muscle cells (SMCs) and collagen. In rabbits, areas of increased 125I-MDA2 uptake were associated with high Sudan concordance and strong immunostaining for OxLDL and macrophages. Interestingly, advanced lesions with focally diminished 125I-MDA2 uptake showed stronger immunostaining for SMCs and collagen, particularly at the fibrous cap.


CONCLUSIONS
Ox-AB uptake is focally diminished in plaques displaying accepted features of plaque stability. Imaging techniques to detect the presence and depletion of OxLDL may be useful in assessing plaque stabilization.
Torzewski
Michael
M
Institute of Clinical Chemistry and Laboratory Medicine, University of Mainz, Germany.
Shaw
Peter X
PX
Han
Kyoo-Rok
KR
Shortal
Brian
B
Lackner
Karl J
KJ
Witztum
Joseph L
JL
Palinski
Wulf
W
Tsimikas
Sotirios
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000918:Antibody Specificity; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis; D000939:Epitopes; D007150:Immunohistochemistry / Q000379:methods; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008077:Lipoproteins, LDL / Q000032:analysis* / Q000276:immunology; D008315:Malondialdehyde; D051379:Mice; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction; D011817:Rabbits; D016719:Radioimmunodetection / Q000379:methods*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde