Abstract
IntroductionThe purpose of this work was to establish and validate combined small animal positron emission tomography - computed tomography (PET/CT) as a new in vivo imaging method for visualisation and quantification of joint inflammation.MethodsSignalling of radioisotope 18F labelled Fluorodeoxyglucose (18F-FDG) injected in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis was analysed by PET/CT. Accumulation of 18F-FDG in tissue was quantified by PET measurement, whereas high definition CT delivered anatomical information. The fusion of both images revealed in detail spatial and temporal distribution and metabolism of 18F-FDG.ResultsA distinct 18F-FDG signal could be measured by PET in carpal and tarsal joints, from mice with early or established arthritis. In contrast, no accumulation of 18F-FDG was detectable before arthritis onset. Comparison of 18F-FDG joint uptake with histopathological evaluation revealed a significant correlation of both methods.ConclusionsSmall animal PET/CT using 18F-FDG is a feasible method for monitoring and, more importantly, quantitative assessment of inflammation in G6PI-arthritis. Since it is possible to perform repeated non-invasive measurements in vivo, not only numbers of animals in preclinical studies can markedly be reduced by this method, but also longitudinal studies come into reach, e. g. for individual flare-up reactions or monitoring therapy response in progressive arthritis.
Highlights
The purpose of this work was to establish and validate combined small animal positron emission tomography - computed tomography (PET/CT) as a new in vivo imaging method for visualisation and quantification of joint inflammation
Histopathological assessment of arthritis severity To examine the usability of state-of-the-art smallanimal Positron emission tomography (PET)/CT molecular imaging as an objective method to quantify inflammation in experimental arthritis research, severity of inflammation was analyzed at six different time points in the course of glucose-6phosphate isomerase (G6PI)-induced arthritis, using both micro-PET/CT and histology
Histopathological assessment of the degree and components of immune cell infiltration, synovial hyperplasia, and exudate in arthritic joints enabled a semiquantitative scoring of experimental arthritis severity (Figure 1a)
Summary
The purpose of this work was to establish and validate combined small animal positron emission tomography - computed tomography (PET/CT) as a new in vivo imaging method for visualisation and quantification of joint inflammation. Non-invasive imaging techniques allowing an objective quantitative assessment of inflammation would, be a most welcome tool for arthritis research. The accumulation of 18F-FDG in cells contributing to synovial inflammation [4,5,6] could provide a sensitive and non-invasive tool for visualization and quantification of joint inflammation in vivo. In rheumatoid arthritis (RA), only a few studies far have examined the use of PET, proposing quantitative 18F-FDG PET as a promising technique to measure disease activity and to monitor the efficacy of anti-inflammatory drugs without restriction to morphology-based information [7,8]. In humans, the detailed morphological information provided by CT can be used to localize the anatomical source of PET signals exactly [10]
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