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Fachbereich Veterinärmedizin



    Molecular imaging of experimental arthritis using an EDB-targeting antibody NIR-dye conjugate (2007)

    Vater, A.
    Gemeinhardt, I.
    Gemeinhardt, O.
    Voigt, J.
    Berger, J.
    Licha, K.
    Vollmer, S.
    Schnorr, J.
    Ebert, B.
    Macdonald, R.
    Taupitz, M.
    Schirner, M.
    Annual European Congress of Rheumatology
    Barcelona/Spain, 13. – 16.06.2007
    Annals of the rheumatic diseases
    Bandzählung: 66
    Heftzählung: Suppl. 2
    Seiten: 300
    ISSN: 0003-4967
    Institut für Veterinär-Anatomie

    Koserstr. 20
    14195 Berlin
    +49 30 838 75784

    Abstract / Zusammenfassung

    Background: <br>Optical imaging is an emerging modality for the detection of lesions without ionizing radiation. Optical imaging probes consisting of a targeting moiety and a fluorescent dye allow molecular imaging approaches, e.g. the specific staining of overexpressed proteins. Fluorescent dyes absorbing and emitting light in the near-infrared (NIR) range of the spectrum (700-900 nm) have proven to be advantageous because of the relative transparency of tissue and blood for this light compared to visible light of shorter wavelengths.

    Collagen-induced arthritis is a model for acute arthritis including synovitis and the formation of an aggressive pannus. The inflammatory hypoxic environment leads to angiogenesis and expression of molecular markers thereof.
    Objectives: <br>We investigated a molecular imaging approach for the detection of collagen-induced arthritis (CIA) in rats by targeting the Extra Domain B (EDB) of the extracellular matrix protein fibronectin. EDB is a highly conserved domain (identical in humans and rats) that is produced by alternative splicing during embryonic development and conditions of vascular remodeling like angiogenesis.
    Methods:<br> We have confirmed the expression of EDB in the hyperplastic synovium of CIA rats by immunohistochemistry. For in vivo diagnostics, the EDB-binding single-chain antibody fragment AP39 was used as a targeting probe (Berndorff et al., 2006). It was covalently linked to the near-infrared (NIR) dye Tetrasulfocyanine (TSC) and visualized by fluorescence reflectance imaging using a 740 nm NIR laser source for excitation and a cooled iCCD-camera for detection. A conjugate consisting of TSC and ovalbumin, having a similar molecular weight as the spontaneously forming AP39-TSC dimer, was used as a control for targeting specificity.
    Results: <br>AP39-TSC induced a significantly enhanced fluorescence contrast in arthritic joints that allowed discrimination from healthy control joints in the CIA-rat model up to 24 h after i.v. application. With ovalbumin-TSC, only a minor accumulation of the conjugate was observed in affected joints. This indicates that the enrichment is due to the specific binding of the probe to EDB.
    Conclusion:<br> Optical imaging using the EDB-binding single-chain antibody fragment AP39 conjugated to the NIR-dye TSC resulted in clear enhancement of fluorescence intensity in affected joints compared to control joints. Since AP39 is a fully human single-chain antibody fragment, a translation of this molecular imaging approach for arthritis detection in man and possibly a repeated use for therapy response monitoring seems feasible.
    References:<br> Berndorff, D., Borkowski, S., Moosmayer, D., Viti, F., Muller-Tiemann, B., Sieger, S., Friebe, M., Hilger, C.S., Zardi, L., Neri, D. and Dinkelborg, L.M. (2006) Imaging of tumor angiogenesis using 99mTc-labeled human recombinant anti-ED-B fibronectin antibody fragments. J Nucl Med, 47, 1707-1716.