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Title
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Characterization of -labeled cytokine ligands for inflammation imaging via TNF and IL-1 pathways
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Author
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Abstract
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| Introduction: TNFR2-Fc and IL-1ra-Fc are recombinant cytokine ligands that target TNF and IL-1. TNFR2-Fc-IL-1ra, a dual-domain agent that incorporates both ligands, allows bifunctional binding of IL-1 receptors and TNF. This study was designed to characterize Tc-99m-labeled forms of these ligands, Tc-99m-IL-1ra-Fc (IF), Tc-99m-TNFR2-Fc (TF), and Tc-99m-TNFR2-Fc-IL-1ra (TFI), for inflammation imaging. Methods: The cytokine ligands were labeled with Tc-99m by a direct approach via 2-iminothiolane (2-IT) reduction at various 2-IT/protein molar ratios. In vivo inflammation targeting studies were carried out in a mouse ear edema model created by topical application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the right ear of ICR mice. Results: Radiolabeling yields increased with increasing amounts of 2-IT. When the 2-IT/protein ratio reached 1000, the radiolabeling yield was greater than 90% without significant colloid production. TPA-treated ears showed high radioligand uptake, which was clearly detected by SPECT and autoradiographic imaging. The activities (%ID/g) in the inflamed and control ears at 3 h after injection were 2.76 +/- 0.20 vs. 0.69 +/- 0.12 for IF, 5.86 +/- 0.40 vs. 2.86 +/- 0.61 for TF, and 7.61 +/- 0.86 vs. 1.99 +/- 0.31 for TFI (P<0.05 vs. controls). TFI showed significantly higher uptake in the inflamed ears compared to TF and IF (P<0.05). Blocking study results indicated specificity of radioligand binding with decreased radioactive uptake in the inflamed ears. Western blotting and ELISA analysis further confirmed a high expression of IL-1 beta and TNF-alpha in the inflamed ears. Conclusions: Tc-99m-labeled cytokine ligands are a promising approach for detecting and understanding the inflammatory process. TFI may be more useful than the single-domain ligands for noninvasive detection of inflammatory sites. (c) 2012 Elsevier Inc. All rights reserved. |
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Language
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English
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Source (journal)
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Nuclear medicine and biology. - Oxford, 1993, currens
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Publication
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Oxford
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2012
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ISSN
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0969-8051
[print]
1872-9614
[online]
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DOI
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10.1016/J.NUCMEDBIO.2012.05.003
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Volume/pages
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39
:7
(2012)
, p. 905-915
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ISI
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000309033800003
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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