Abstract
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Objectives Current treatment of rheumatoid arthritis includes systemic administration of corticoids. Liposomal encapsulation of corticoids improves joint targeting and anti-inflammatory efficacy. We aimed to monitor therapeutic effect of prednisolon phosphate (PLP)-containing liposomes in murine antigen-induced arthritis (AIA) using 18F-FDG PET/CT.
Methods Mono-articular arthritis was induced in male C57Bl6/J mice. At 0, 3, 7 and 12 days after arthritis induction, inflamed joints were macroscopically scored (0=unaffected - 4=immobile) and 18F-FDG PET/CT images were acquired. In a second experiment, to study the feasibility to monitor therapeutic effects, mice were treated with a single i.v. injection of PLP-containing liposomes (10 mg/kg) or empty liposomes 3 days after arthritis induction. Inflamed joints were macroscopically scored and 18F-FDG PET/CT images were acquired at -3, 0, 4 and 9 days after treatment. 18F-FDG uptake was quantified, and mice were dissected to allow histological analysis of the joints
Results With progression of arthritis, 18F-FDG uptake in inflamed joints increased significantly (day 0: 2.5±0.9 %ID/g, day 7: 4.4±0.4 %ID/g, p=0.02), while no changes were observed in unaffected paws (day 0: 2.5±1.1 %ID/g, day 7: 2.7±0.8 %ID/g). In the second experiment, macroscopic scoring revealed suppression of joint swelling. In line with that, 18F-FDG uptake did not change (day -3: 1.9±0.3 %ID/g, day 4: 2.2±0.2 %ID/g, p=0.347), but increased in control mice (day -3: 2.0±0.2 %ID/g, day 4: 3.1±0.6 %ID/g, p=0.02). Histological analysis confirmed therapeutic efficacy, which showed less inflammation (p=0.035) and bone erosion (p=0.03) in treated mice.
Conclusions 18F-FDG PET/CT could be used to monitor the progression of AIA and the anti-inflammatory effects of PLP-containing liposomes at an early stage.
Research Support NanoNextNL 03D.06