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

T. van der Geest, J. Metselaar, D. Gerrits, P. van Lent, G. Storm, P. Laverman and O. Boerman

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Geert Grooteplein zuid 10, 6525 GA Nijmegen, The Netherlands. Electronic address: Otto.Boerman@radboudumc.nl.
Apr, 2015



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 [(18)F]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 [(18)F]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, [(18)F]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, [(18)F]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 [(18)F]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.