Abstract
BackgroundIn 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.MethodsMice 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.ResultsExplicit 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.ConclusionsThe 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.
Highlights
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
In the present study, we focused on longitudinal quantitative PET/computed tomography (CT) imaging with the VAP-1-targeting tracer 68Ga-DOTA-Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 to assess B. burgdorferi infectioninduced inflammation in mice, with particular emphasis on the arthritic joints
We have demonstrated that 68Ga-DOTA-Sigec-9 can accurately detect B. burgdorferi infection-induced arthritis in mice
Summary
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. There are a few in vivo imaging techniques that can be used to monitor B. burgdorferi infection in mice, these techniques have some disadvantages. Offering an alternative to current in vivo imaging techniques, positron emission tomography (PET) allows longitudinal imaging of individual mice at several time points. This presents the opportunity to visualize and quantify the status of specific organs; monitor the dissemination of an infection; and use wild-type and unlabeled bacteria, which is especially important
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