Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo

We investigated a molecular imaging approach for the detection of collagen-induced arthritis in rats by targeting the extra domain B (ED-B) of the extracellular matrix protein fibronectin. ED-B is a highly conserved domain (identical in human and rats) that is produced by alternative splicing during...

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Main Authors: Sonja Vollmer, Axel Vater, Kai Licha, Ines Gemeinhardt, Ole Gemeinhardt, Jan Voigt, Bernd Ebert, Jörg Schnorr, Matthias Taupitz, Rainer Macdonald, Michael Schirner
Format: Article
Language:English
Published: SAGE Publishing 2009-11-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2009.00030
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author Sonja Vollmer
Axel Vater
Kai Licha
Ines Gemeinhardt
Ole Gemeinhardt
Jan Voigt
Bernd Ebert
Jörg Schnorr
Matthias Taupitz
Rainer Macdonald
Michael Schirner
author_facet Sonja Vollmer
Axel Vater
Kai Licha
Ines Gemeinhardt
Ole Gemeinhardt
Jan Voigt
Bernd Ebert
Jörg Schnorr
Matthias Taupitz
Rainer Macdonald
Michael Schirner
author_sort Sonja Vollmer
collection DOAJ
description We investigated a molecular imaging approach for the detection of collagen-induced arthritis in rats by targeting the extra domain B (ED-B) of the extracellular matrix protein fibronectin. ED-B is a highly conserved domain (identical in human and rats) that is produced by alternative splicing during embryonic development and during vascular remodeling such as angiogenesis. The hallmark of rheumatoid arthritis is synovitis leading to both angiogenesis in the synovium and the promotion of cartilage and bone disruption. For in vivo diagnostics, the ED-B-binding single-chain antibody fragment AP39 was used as a targeting probe. It was covalently linked to the near-infrared dye tetrasulfocyanine (TSC) to be visualized by near-infrared fluorescence imaging. The resulting AP39-TSC conjugate was intravenously administered to rats with collagen-induced arthritis and the respective controls. Ovalbumin-TSC was used as control conjugate. Optical imaging over a time period of 24 hours using a planar imaging setup resulted in a clear enhancement of fluorescence intensity in joints with moderate to severe arthritis compared with control joints between 3 and 8 hours postinjection. Given that AP39 is a fully human antibody fragment, this molecular imaging approach for arthritis detection might be translated to humans.
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spelling doaj-art-e257d9b268034a2e85e9de52035a7a582025-01-02T02:58:21ZengSAGE PublishingMolecular Imaging1536-01212009-11-01810.2310/7290.2009.0003010.2310_7290.2009.00030Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In VivoSonja VollmerAxel VaterKai LichaInes GemeinhardtOle GemeinhardtJan VoigtBernd EbertJörg SchnorrMatthias TaupitzRainer MacdonaldMichael SchirnerWe investigated a molecular imaging approach for the detection of collagen-induced arthritis in rats by targeting the extra domain B (ED-B) of the extracellular matrix protein fibronectin. ED-B is a highly conserved domain (identical in human and rats) that is produced by alternative splicing during embryonic development and during vascular remodeling such as angiogenesis. The hallmark of rheumatoid arthritis is synovitis leading to both angiogenesis in the synovium and the promotion of cartilage and bone disruption. For in vivo diagnostics, the ED-B-binding single-chain antibody fragment AP39 was used as a targeting probe. It was covalently linked to the near-infrared dye tetrasulfocyanine (TSC) to be visualized by near-infrared fluorescence imaging. The resulting AP39-TSC conjugate was intravenously administered to rats with collagen-induced arthritis and the respective controls. Ovalbumin-TSC was used as control conjugate. Optical imaging over a time period of 24 hours using a planar imaging setup resulted in a clear enhancement of fluorescence intensity in joints with moderate to severe arthritis compared with control joints between 3 and 8 hours postinjection. Given that AP39 is a fully human antibody fragment, this molecular imaging approach for arthritis detection might be translated to humans.https://doi.org/10.2310/7290.2009.00030
spellingShingle Sonja Vollmer
Axel Vater
Kai Licha
Ines Gemeinhardt
Ole Gemeinhardt
Jan Voigt
Bernd Ebert
Jörg Schnorr
Matthias Taupitz
Rainer Macdonald
Michael Schirner
Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo
Molecular Imaging
title Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo
title_full Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo
title_fullStr Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo
title_full_unstemmed Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo
title_short Extra Domain B Fibronectin as a Target for Near-Infrared Fluorescence Imaging of Rheumatoid Arthritis Affected Joints In Vivo
title_sort extra domain b fibronectin as a target for near infrared fluorescence imaging of rheumatoid arthritis affected joints in vivo
url https://doi.org/10.2310/7290.2009.00030
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