A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Targeting of vascular adhesion protein-1 by positron emission tomography visualizes sites of inflammation in Borrelia burgdorferi-infected mice




TekijätRiikka Siitonen, Annukka Pietikäinen, Heidi Liljenbäck, Meeri Käkelä, Mirva Söderström, Sirpa Jalkanen, Jukka Hytönen, Anne Roivainen

KustantajaBIOMED CENTRAL LTD

KustannuspaikkaLONDON

Julkaisuvuosi2017

JournalArthritis Research and Therapy

Tietokannassa oleva lehden nimiARTHRITIS RESEARCH & THERAPY

Lehden akronyymiARTHRITIS RES THER

Artikkelin numero254

Vuosikerta19

Sivujen määrä10

ISSN1478-6354

DOIhttps://doi.org/10.1186/s13075-017-1460-4

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/27386389


Tiivistelmä
Background: In the present study, we sought to evaluate the feasibility of targeting vascular adhesion protein-1 (VAP-1) by positron emission tomography (PET) for the longitudinal quantitative assessment of Borrelia burgdorferi infection-induced inflammation in mice.Methods: Mice with B. burgdorferi infection-induced arthritis were studied. During a 7-week follow-up period, the progression of arthritis was monitored weekly with 68Ga-DOTA-Siglec-9 PET/computed tomography (CT) and measurement of tibiotarsal joint swellings. A subgroup of infected mice was treated with ceftriaxone. Finally, histopathological assessment of joint inflammation was performed and VAP-1 expression in joints were determined.Results: Explicit joint swelling and 68Ga-DOTA-Siglec-9 uptake could be demonstrated in the affected joints from B. burgdorferi-infected mice. By contrast, no obvious accumulation of 68Ga-DOTA-Siglec-9 was detected in joints of uninfected mice. The maximum swelling and highest uptake in the affected joints were observed 4 weeks after the infection. 68Ga-DOTA-Siglec-9 uptake in joints correlated with joint swelling (P < 0.0001) and histopathological scoring of inflammation (P = 0.020). Despite short-term antibiotic treatment, the arthritis persisted, and the PET signal remained as high as in nontreated mice. Immunohistochemistry revealed strong-to-moderate expression of VAP-1 in the synovium of B. burgdorferi-infected mice, while only weak expression of VAP-1 was detected in uninfected mice.Conclusions: The present study showed that 68Ga-DOTA-Siglec-9 can detect B. burgdorferi infection-induced arthritis in mice. Furthermore, longitudinal PET/CT imaging allowed monitoring of arthritis development over time.

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