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

• Published in: Arthritis research & therapy Vol. 19; no. 1; p. 254
• Main Authors: Siitonen, Riikka, Pietikäinen, Annukka, Liljenbäck, Heidi, Käkelä, Meeri, Söderström, Mirva, Jalkanen, Sirpa, Hytönen, Jukka, Roivainen, Anne
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.11.2017; BioMed Central; BMC
• Subjects: Antibiotics; Arthritis; Bacterial infections; Borrelia burgdorferi; Cellular proteins; Experiments; Health aspects; Histology; Infection; Infections; Inflammation; Lyme borreliosis; Lyme disease; Medical diagnosis; Medical imaging; Medical research; Nuclear medicine; Peptides; PET; PET imaging; Proteins; Tomography; Tuberculosis; Finland; Infection; Lyme borreliosis; Siglec-9; Borrelia burgdorferi; VAP-1; arthritis; Inflammation; PET
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-017-1460-4

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. Mice with B. burgdorferi infection-induced arthritis were studied. During a 7-week follow-up period, the progression of arthritis was monitored weekly with Ga-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. Explicit joint swelling and Ga-DOTA-Siglec-9 uptake could be demonstrated in the affected joints from B. burgdorferi-infected mice. By contrast, no obvious accumulation of Ga-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. Ga-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. The present study showed that Ga-DOTA-Siglec-9 can detect B. burgdorferi infection-induced arthritis in mice. Furthermore, longitudinal PET/CT imaging allowed monitoring of arthritis development over time.