Abstract
Macrophages play a key role in the inflammatory response in Lyme arthritis (LA) and could be a target for diagnosing and monitoring active Borrelia burgdorferi sensu lato (Bb) infection. Therefore, we evaluated the potential of macrophage imaging using 64Cu-DOTATATE PET/CT for detection of Bb activity in a murine model of LA. LA was established in C3H/HeNRj mice infected with Bb B31 strain ML23 pBBE22luc. Bioluminescence imaging was performed to detect migration of spirochetes and inflammatory phagocytes to the joints. Three weeks post-infection 64Cu-DOTATATE PET/CT imaging was performed at an early (3 h) and late (48 h) time point. Plasma levels of a systemic macrophage marker in plasma CD163 were measured. 64Cu-DOTATATE uptake in infected joints was increased at the early (p < 0.0001) and late time points (p = 0.0005) compared with uptake in non-infected controls. No significant difference in plasma levels of CD163 was measured. 64Cu-DOTATATE PET allows for in vivo detection and quantification of LA locally in the joints through non-invasive visualization of macrophages. In contrast, measurement of a systemic macrophage marker in plasma, CD163, did not allow to detect disease. We suggest that 64Cu-DOTATATE PET could become a valuable diagnostic tool for in situ detection of Bb infection-related inflammation.
Highlights
Lyme borreliosis (LB) caused by the Borrelia burgdorferi sensu lato (Bb s.l.) complex is the most prevalent vector-borne infection in Europe and the US with estimates of annual incidence ranging fromDiagnostics 2020, 10, 790; doi:10.3390/diagnostics10100790 www.mdpi.com/journal/diagnostics10–80 per 100,000 inhabitants
The major finding in the present study was that imaging using tracer demonstrating macrophages, could detect and monitor Lyme arthritis activity non-invasively, tracer demonstrating macrophages, detect and
We showed that 64 Cu-DOTATATE can be used in another inflammatory model as the tracer significantly accumulates in the joints of collagen-induced arthritis (CIA) mice with high clinical score at an early time point
Summary
Lyme borreliosis (LB) caused by the Borrelia burgdorferi sensu lato (Bb s.l.) complex is the most prevalent vector-borne infection in Europe and the US with estimates of annual incidence ranging fromDiagnostics 2020, 10, 790; doi:10.3390/diagnostics10100790 www.mdpi.com/journal/diagnostics10–80 per 100,000 inhabitants. Bb s.l. can cause a variety of clinical manifestations including erythema migrans, Lyme neuroborreliosis and Lyme arthritis. Whereas B. garinii and B. afzelii cause Lyme neuroborreliosis and dermatoborreliosis, respectively [1,2,3]. A diagnosis of disseminated LB is based on possible exposure to tick bites, compatible clinical symptoms and objective signs in combination with antibody detection [4]. Seropositivity alone is insufficient to make a diagnosis of active LB, as antibodies may first be detectable after weeks of infection and may persist for years after the infection has been treated. Borrelia DNA can persist for months in the skin or in synovial fluid even after successful treatment, which renders the difficulty for direct detection of Borrelia DNA to unequivocally verify an active infection [5,6,7]. New methods to monitor disease activity in patients with LB would be of paramount interest to practice precision medicine in these patients and to promote a shift from empirical treatment to personalized medicine with expected improvement in patient outcome
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