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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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123I-Anti-vascular cell adhesion molecule monoclonal antibody 5F10

123I-5F10
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: October 29, 2007.

Chemical name:123I-Anti-vascular cell adhesion molecule monoclonal antibody 5F10
Abbreviated name:123I-5F10
Synonym:
Agent Category:Antibody
Target:Vascular cell adhesion molecule-1 (VCAM-1)
Target Category:Antibody-antigen binding
Method of detection:SPECT, gamma planar imaging
Source of signal:123I
Activation:No
Studies:
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about VCAM-1.

Background

[PubMed]

Endothelial cells are important in inflammatory responses (1, 2). Bacterial lipopolysaccharide (LPS), virus, inflammation, and tissue injury increase tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and other cytokine and chemokine secretion. Emigration of leukocytes from blood is dependent on their ability to roll along endothelial cell surfaces and subsequently adhere to endothelial cell surfaces. Inflammatory mediators and cytokines induce chemokine secretion from endothelial cells and other vascular cells and increase their expression of cell-surface adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), integrins, and selectins. Chemokines are chemotactic toward leukocytes and sites of inflammation and tissue injury. The movement of leukocytes through endothelial junctions into the extravascular space are highly orchestrated through various interactions with different adhesion molecules on endothelial cells (3).

VCAM-1 is found in very low levels on the cell surface of resting endothelial cells and other vascular cells, such as smooth muscle cells and fibroblasts (4-8). VCAM-1 binds to its counterligand, very late antigen-4 (VLA-4) integrin, on the cell surface of leukocytes. IL-1 and TNFα increase expression of VCAM-1 and other cell adhesion molecules on the vascular endothelial cells, which leads to leukocyte adhesion to the activated endothelium. Furthermore, VCAM-1 expression was also induced by oxidized low-density lipoproteins under atherogenic conditions (9). Overexpression of VCAM-1 by atherosclerotic lesions plays an important role in their progression toward vulnerable plaques, which may erode and rupture. 5F10 is a murine monoclonal antibody (mAb) against rat VCAM-1 (10). 123I-Labeled 5F10 (123I-5F10) is being developed as a non-invasive tool for VCAM-1 expression in vascular endothelial cells in experimental colitis (11).

Synthesis

[PubMed]

The 5F10 mAb (1.67 nmol) was labeled with 15–25 MBq (0.41–0.68 mCi) [123I]NaI in the presence of tetrachlorodiphenylglycoluril (Iodogen) (11). 123I-5F10 was purified by gel filtration with <1% free 123I. No specific activity or radiochemical yield was reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

No publication is currently available.

Animal Studies

Rodents

[PubMed]

Sans et al. (11) performed biodistribution and scintigraphic studies of 123I-5F10 in control and colitic rats. In colitic rats, the organ with the highest mAb accumulation at 4 h after injection was the spleen (1,164.5 ng/g), followed by the colon (140 ± 30 ng/g), kidneys (96.5 ± 11.3 ng/g), ileum (48.8 ± 10.8 ng/g), and lungs (45.5 ± 4.0 ng/g). There were no differences between control and colitic rats in any of the extra-colonic organs studied. Only 20 ± 1 ng/g mAb accumulated in the colon of control rats. The accumulation of control antibody was significantly lower than control or colitic rats in all organ studies. Pretreatment with 5F10 decreased accumulation of 125I-5F10 by 80% in the colitic colon and by 40–75% in the other organs studied. Scintigraphic images were obtained in control and colitic rats at 2, 4, and 24 h after 123I-5F10 injection. The colon was clearly visible at 2–24 h in the colitic rats but not in the control rats. However, the liver and spleen were visible in both control and colitic rats. Pretreatment with 5F10 completely prevented the signal in the colon in the colitic rats at 2–24 h. The colon scintigraphic uptake correlated significantly (P < 0.01) with histological damage scores and with neutrophil infiltration.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Cybulsky M.I. , Gimbrone M.A. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991;251(4995):788–91. [PubMed: 1990440]
2.
Lowe J.B. Glycosylation in the control of selectin counter-receptor structure and function. Immunol Rev. 2002;186:19–36. [PubMed: 12234359]
3.
Vanderslice P. , Woodside D.G. Integrin antagonists as therapeutics for inflammatory diseases. Expert Opin Investig Drugs. 2006;15(10):1235–55. [PubMed: 16989599]
4.
Bochner B.S. , Luscinskas F.W. , Gimbrone M.A. , Newman W. , Sterbinsky S.A. , Derse-Anthony C.P. , Klunk D. , Schleimer R.P. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med. 1991;173(6):1553–7. [PMC free article: PMC2190849] [PubMed: 1709678]
5.
Kume N. , Cybulsky M.I. , Gimbrone M.A. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest. 1992;90(3):1138–44. [PMC free article: PMC329976] [PubMed: 1381720]
6.
Leung K.H. Release of soluble ICAM-1 from human lung fibroblasts, aortic smooth muscle cells, dermal microvascular endothelial cells, bronchial epithelial cells, and keratinocytes. Biochem Biophys Res Commun. 1999;260(3):734–9. [PubMed: 10403835]
7.
Luscinskas F.W. , Cybulsky M.I. , Kiely J.M. , Peckins C.S. , Davis V.M. , Gimbrone M.A. Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. J Immunol. 1991;146(5):1617–25. [PubMed: 1704400]
8.
Nagel T. , Resnick N. , Atkinson W.J. , Dewey C.F. , Gimbrone M.A. Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J Clin Invest. 1994;94(2):885–91. [PMC free article: PMC296171] [PubMed: 7518844]
9.
Aikawa M. , Libby P. The vulnerable atherosclerotic plaque: pathogenesis and therapeutic approach. Cardiovasc Pathol. 2004;13(3):125–38. [PubMed: 15081469]
10.
Sans M. , Panes J. , Ardite E. , Elizalde J.I. , Arce Y. , Elena M. , Palacin A. , Fernandez-Checa J.C. , Anderson D.C. , Lobb R. , Pique J.M. VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis. Gastroenterology. 1999;116(4):874–83. [PubMed: 10092309]
11.
Sans M. , Fuster D. , Vazquez A. , Setoain F.J. , Piera C. , Pique J.M. , Panes J. 123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis. Eur J Gastroenterol Hepatol. 2001;13(1):31–8. [PubMed: 11204806]

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