18]F FDG PET/CT imaging to monitor the therapeutic effect of liposome-encapsulated prednisolone in experimental rheumatoid arthritis

Abstract

Current treatment of rheumatoid arthritis includes systemic administration of glucocorticoids. To improve joint targeting and anti-inflammatory efficacy these glucocorticoids are encapsulated in long-circulating liposomes. The present study aimed to monitor therapeutic effects of prednisolone (PLP)-containing PEG-liposomes in murine antigen-induced arthritis (AIA) using [18F]FDG PET/CT.Mono-articular arthritis was induced in male C57Bl6/J mice. At 0, 3, 7 and 12days after arthritis induction, inflamed joints were macroscopically scored (0=unaffected to 4=immobile) and [18F]FDG PET/CT images were acquired. In a second experiment, to study the feasibility to monitor therapeutic effects of PLP encapsulating PEG-liposomes, mice were treated with a single i.v. injection of PLP-containing PEG-liposomes (10mg/kg) or empty PEG-liposomes 3days after arthritis induction. Inflamed joints were macroscopically scored and images were acquired at −3, 0, 4 and 9days after treatment. PET images were analyzed quantitatively, and mice were dissected to allow histological analysis of the joints. With progression of arthritis, [18F]FDG uptake in inflamed joints increased significantly (day 0: 2.5±0.9%ID/ml, day 7: 4.4±0.4%ID/ml, p=0.0159), while no changes were observed in unaffected paws (day 0: 2.5±1.1%ID/ml, day 7: 2.7±0.8%ID/ml, p=0.3466). In the second experiment, macroscopic scoring revealed suppression of joint swelling after treatment with PLP-containing PEG-liposomes. In line with that, [18F]FDG uptake did not change in the treated mice (day −3: 1.9±0.3%ID/ml, day 4: 2.2±0.2%ID/ml, p=0.3466), while it increased in mice that developed arthritis (day −3: 2.0±0.2%ID/ml, day 4: 3.1±0.6%ID/ml, p=0.0225). Histological analysis confirmed therapeutic efficacy, which showed less inflammation (p=0.0354) and bone erosion (p=0.0298) in treated mice. These data show that [18F]FDG PET/CT could be used to monitor the progression of AIA and confirmed rapid and profound anti-inflammatory effects of PLP-containing PEG-liposomes that were also observed macroscopically and microscopically.