In vivo imaging of Lyme arthritis in mice by [¹⁸F]fluorodeoxyglucose positron emission tomography/computed tomography

Abstract

Objective: Lyme borreliosis (LB) is a tick-borne infectious disease caused by Borrelia burgdorferi spirochaetes, which are able to disseminate from the tick-bite site to distant organs. Mouse models are widely used to study LB and especially Lyme arthritis (LA), but only a few whole-animal in vivo imaging studies on the pathogenesis of B. burgdorferi infection in mice have been published so far. The existing imaging techniques have their drawbacks and, therefore, novel tools to complement the array of available LB imaging methodologies are needed.

Method: The applicability of positron emission tomography combined with computed tomography (PET/CT) imaging was evaluated as a method to monitor LB and especially LA in the C3H/HeN mouse model infected with wild-type B. burgdorferi N40 bacteria. The imaging results were compared with the traditional LA analysis methods, such as tibiotarsal joint swelling and histopathological assessment of joint inflammation.

Results: PET/CT imaging provided high-resolution images with quantitative information on the spatial and temporal distribution of the [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) tracer in B. burgdorferi-infected mice. The [¹⁸F]FDG accumulated in the affected joints and activated lymph nodes of infected mice, while the tracer signal could not be visualized in these organs in uninfected control animals. Importantly, in vivo PET/CT imaging data were in agreement with the histopathological scoring of inflammation of mouse joints.

Conclusion: PET/CT imaging with [¹⁸F]FDG is a reliable method to longitudinally monitor the development and progression of B. burgdorferi infection-induced inflammation in vivo in mouse joints.

Acknowledgements

Erica Nyman and Aake Honkaniemi are thanked for technical assistance. Juho Vuononvirta and Julia Honkasalo are thanked for helping with the mice.

The study was financially supported by the Academy of Finland, a grant from Turku University Hospital (Diagnostics and Related Services), the Drug Research Doctoral Programme of the University of Turku Graduate School, and the Turku Doctoral Programme for Molecular Medicine of the University of Turku Graduate School. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Additional information

Funding

This work was supported by the Drug Research Doctoral Programme of the University of Turku Graduate School: [Grant Number xxxx, xxx].