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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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125I-Anti-malondialdehyde-modified low-density lipoprotein monoclonal antibody

125I-MDA2
, PhD
National for Biotechnology Information, NLM, NIH, Bethesda, MD

Created: ; Last Update: October 22, 2009.

Chemical name:125I-Anti-malondialdehyde-modified low-density lipoprotein monoclonal antibody
Abbreviated name:125I-MDA2
Synonym:
Agent category:Antibody
Target:Malondialdehyde-modified low-density lipoprotein (MDA-LDL)
Target category:Antigen
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar imaging
Source of signal/contrast:125I
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
  • Checkbox Other non-primate mammals
Click on protein, nucleotide (RefSeq), and gene for more information about apolipoprotein B.

Background

[PubMed]

Apolipoprotein E (apoE) is essential for the normal catabolism of triglyceride-rich lipoprotein chylomicrons (lipoprotein particles) (1). Oxidation of low-density lipoprotein (LDL) generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoliprotein B and other proteins. Oxidized LDL is present in atherosclerotic lesions and is essential for formation of foam cells in atherosclerotic plaques. During atherogenic conditions, depositions of lipids and extracellular matrix proteins on the endothelial cell surfaces of the aorta and cells lead to the development of atherosclerotic plaques (2), which may erode and rupture. MDA2 is a murine monoclonal antibody (mAb) to malondialdehyde-lysine epitopes of MDA-LDL and other oxidatively modified proteins but not to normal LDL (3). Tsimikas and colleagues (4-6) have studied 125I-MDA2 for imaging atherosclerotic plaques in small animals.

Synthesis

[PubMed]

MDA2 was labeled with 125I via the lactoperoxidase/glucose oxidase method (5). 125I-MDA2 had a specific activity of 555 MBq/µmol (15 mCi/µmol).

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

125I-MDA2 has been shown to bind specifically to human MDA-LDL but not to normal human LDL, high-density lipoprotein, very low-density lipoprotein, or bovine serum albumin (5).

Animal Studies

Rodents

[PubMed]

Tsimikas et al. (6) measured accumulation of 125I-MDA2 in the aorta of 6-month-old LDLR-/- knockout mice that were fed a high-fat, high-cholesterol diet (n = 9 mice), a normal chow diet (n = 8 mice), or a normal chow diet supplemented with vitamin E+C (n = 9 mice) for 6 months. The aortic weight was 35, 18, and 15 mg, respectively. The percent of injected dose was 0.14 ± 0.03, 0.03 ± 0.01, and 0.03 ± 0.01, respectivelyat 24 h after injection. There was a high amount of oxidized LDL in the aorta of mice fed the high-fat diet.

Other Non-Primate Mammals

[PubMed]

Tsimikas et al. (5) performed ex vivo assessment of 125I-MDA2 for atherosclerotic lesions in LDL receptor–deficient Watanabe heritable hyperlipidemic rabbits (WHHL, n = 7) and normal New Zealand white rabbits (NZW, n = 2) at 24 h after injection. 125I-Halb, an isotype-matched irrelevant mAb that binds to human albumin, was used as a control. The blood half-life was 12 h for 125I-MDA2 and 9 h for 125I-Halb in both WHHL and NZW rabbits. Aortic autoradiography was performed, and the mean uptake of mAbs was measured as the percent of injected dose per gram (% ID/g) of aortic tissueat 24 h after injection. Mean uptake of 125I-MDA2 in the entire aorta (0.09% ID/g) was 17.4-fold higher in WHHL than in NZW aortas (P < 0.001) and 2.8-fold higher than mean uptake of 125I-Halb in the WHHL aortas (P < 0.01). 125I-MDA2 also had higher specificity for lesioned areas than did 125I-Halb (plaque/normal ratio, 6.3 versus 2.9, P < 0.001). Autoradiographic analysis of aortasat 24 h after injection from NZW rabbits injected with 125I-MDA2 did not yield any visible signal. Injection of 10 mg MDA-LDL 24 h after injection of 125I-MDA2 in WHHL rabbits reduced the residual blood radioactivity from 31% to 7.5% (P < 0.001). There was no significant difference in the aortic accumulation in the two groups; however, there was an improvement in the plaque/blood ratio from 0.6 to 1.4. Autoradiographs of aortas of 125I-MDA2-injected WHHL rabbits revealed uptake in lipid-stained lesions with an absence of signal in adjacent normal arterial tissue. Immunostaining of WHHL lesions revealed that uptake was highest in areas with abundant foam cells and in lipid-rich necrotic core areas.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

NIH Support

HL07444, HL03793, HL14197, HL05989

References

1.
Eichner J.E., Dunn S.T., Perveen G., Thompson D.M., Stewart K.E., Stroehla B.C. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol. 2002;155(6):487–95. [PubMed: 11882522]
2.
Libby P., Ridker P.M., Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135–43. [PubMed: 11877368]
3.
Palinski W., Yla-Herttuala S., Rosenfeld M.E., Butler S.W., Socher S.A., Parthasarathy S., Curtiss L.K., Witztum J.L. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 1990;10(3):325–35. [PubMed: 1693068]
4.
Tsimikas S. Noninvasive imaging of oxidized low-density lipoprotein in atherosclerotic plaques with tagged oxidation-specific antibodies. Am J Cardiol. 2002;90(10C):22L–27L. [PubMed: 12459423]
5.
Tsimikas S., Palinski W., Halpern S.E., Yeung D.W., Curtiss L.K., Witztum J.L. Radiolabeled MDA2, an oxidation-specific, monoclonal antibody, identifies native atherosclerotic lesions in vivo. J Nucl Cardiol. 1999;6(1 Pt 1):41–53. [PubMed: 10070840]
6.
Tsimikas S., Shortal B.P., Witztum J.L., Palinski W. 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. Arterioscler Thromb Vasc Biol. 2000;20(3):689–97. [PubMed: 10712392]
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