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    Molecular MR-imaging for noninvasive quantification of the anti-inflammatory effect of targeting interleukin-1β in a mouse model of aortic aneurysm (2020)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Brangsch, Julia (WE 11)
    Reimann, Carolin (WE 11)
    Kaufmann, Jan Ole
    Adams, Lisa Christine
    Onthank, David
    Thöne-Reineke, Christa (WE 11)
    Robinson, Simon
    Wilke, Marco
    Weller, Michael
    Buchholz, Rebecca
    Karst, Uwe
    Botnar, Rene
    Hamm, Bernd
    Makowski, Marcus Richard
    Quelle
    Molecular imaging : official journal of the Society for Molecular Imaging
    Bandzählung: 19
    Seiten: Artikel 1536012120961875
    ISSN: 1536-0121
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://journals.sagepub.com/doi/pdf/10.1177/1536012120961875
    DOI: 10.1177/1536012120961875
    Pubmed: 33216687
    Kontakt
    Institut für Tierschutz, Tierverhalten und Versuchstierkunde

    Königsweg 67
    14163 Berlin
    +49 30 838 61146
    tierschutz@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Background:
    Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.

    Methods:
    Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).

    Results:
    Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R2 = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R2 = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.

    Conclusions:
    Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.