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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-Arg-Glu-Asn-Leu-Arg-Ile-Ala-Leu-Arg-Tyr

123I-B2702-p
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: November 15, 2007.

Chemical name:123I-Arg-Glu-Asn-Leu-Arg-Ile-Ala-Leu-Arg-Tyr
Abbreviated name:123I-B2702-p
Synonym:123I-RENLRIALRY
Agent Category:Peptide
Target:Vascular cell adhesion molecule-1 (VCAM-1)
Target Category:Receptor binding
Method of detection:SPECT, gamma planar imaging
Source of signal:123I
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about VCAM-1.

Background

[PubMed]

Endothelial cells are important cells in inflammatory responses (1, 2). Bacterial lipopolysaccharides (LPS), viruses, inflammation, and tissue injury increase secretion of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and other cytokines and chemokines. 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 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), integrins, and selectins. Chemokines are chemotactic toward leukocytes and sites of inflammation and tissue injury. The movements 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 (often non-detectable) 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 integrin, very late antigen-4 (VLA-4), on the cell surface of leukocytes. Inflammatory cytokines, such as IL-1 and TNF-α, 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 (1). Overexpression of VCAM-1 by atherosclerotic lesions plays an important role in their progression toward vulnerable plaques, which may erode and rupture. A synthetic peptide (Arg-Glu-Asn-Leu-Arg-Ile-Ala-Leu-Arg-Tyr, B2702-p) corresponding to residues 75–84 of HLA-B2702 was shown to bind specifically to VCAM-1 (9). 123I-Labelingof B2702-p was performed on the tyrosine (residue 84) using the chloramine-T method (10). 123I-labeled B2702-p is being developed as a non-invasive agent for VCAM-1 expression in vascular endothelial cells during different stages of inflammation in atherosclerosis.

Synthesis

[PubMed]

B2702-p (prepared by solid-phase synthesis) was labeled with sodium [123I]iodide by electrophilic radioiodination using the chloramine-T method (10). A total of 200 MBq (5.41 mCi) 123I was added to 20–40 nmol B2702-p in the presence of 20–80 μg chloramine T. The reaction was stopped after 15 min. 123I-B2702-p was purified by anion exchange column chromatography. No yield, specific activity, or radiochemical purity values were reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

Fluorescence polarization experiments estimated a Kd value of 270 nM for the interaction between VCAM-1 and B2702-p (10).

Animal Studies

Rodents

[PubMed]

Broisat et al. (10) reported studies of 123I- or 99mTc-labeled B2702-p uptake into aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits (n = 6) and control animals (n = 6) by ex vivo autoradiographic imaging, gamma counting, VCAM-1 immunohistology, and Sudan IV lipid staining at 180 min after injection. Robust VCAM-1 immunostaining was observed in Sudan IV–positive and to a lesser extent in Sudan IV–negative areas of WHHL rabbits, whereas no expression was detected in control rabbits. 123I-B2702-p exhibited a 2.9-fold increase in aortic/blood ratios between WHHL and control rabbits (P < 0.05), whereas 99mTc-B2702-p showed a 1.9-fold increase (P < 0.05). Both tracer uptakes on ex vivo images co-localized with atherosclerotic plaques. Image quantification indicated a graded increase in 123I-B2702-p and 99mTc-B2702-p activities from control to Sudan IV–negative and to Sudan IV–positive areas, correlating to the observed pattern of VCAM-1 expression. Sudan IV–positive tracer activity to control area tracer activity ratios were 17.0 ± 9.0 and 5.9 ± 1.8 for 123I-B2702-p and 99mTc-B2702-p, respectively. No significant difference was observed in 123I-B2702-p and 99mTc-B2702-p radioactivity between control and WHHL rabbits in all other organs examined. The kidneys (0.307 ± 0.052 versus 0.490 ± 0.184) and lungs (0.138 ± 0.028 versus 0.163 ± 0.044) were the major organs for 123I-B2702-p accumulation, whereas the kidneys (0.558 ± 0.109 versus 1.361 ± 0.721), livers (0.427 ± 0.080 versus 0.332 ± 0.042), and lungs (0.166 ± 0.052 versus 0.208 ± 0.044) were the major organs for 99mTc-B2702-p accumulation. No blocking experiments were performed.

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.
Ling X. , Tamaki T. , Xiao Y. , Kamangar S. , Clayberger C. , Lewis D.B. , Krensky A.M. An immunosuppressive and anti-inflammatory HLA class I-derived peptide binds vascular cell adhesion molecule-1. Transplantation. 2000;70(4):662–7. [PubMed: 10972226]
10.
Broisat A. , Riou L.M. , Ardisson V. , Boturyn D. , Dumy P. , Fagret D. , Ghezzi C. Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p. Eur J Nucl Med Mol Imaging. 2007;34(6):830–40. [PubMed: 17219135]

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