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[(18)]F FDG PET/CT imaging to monitor the therapeutic effect of liposome-encapsulated prednisolone in experimental rheumatoid arthritis.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2015 Jul 10; Vol. 209, pp. 20-6. Date of Electronic Publication: 2015 Apr 19. - Publication Year :
- 2015
-
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 [(18)F]FDG PET/CT. 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 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 (10 mg/kg) or empty PEG-liposomes 3 days after arthritis induction. Inflamed joints were macroscopically scored and images were acquired at -3, 0, 4 and 9 days 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.<br /> (Copyright © 2015. Published by Elsevier B.V.)
- Subjects :
- Adjuvants, Immunologic
Animals
Arthritis, Experimental drug therapy
Arthritis, Experimental metabolism
Arthritis, Experimental pathology
Arthritis, Rheumatoid drug therapy
Arthritis, Rheumatoid metabolism
Arthritis, Rheumatoid pathology
Bordetella pertussis
Disease Progression
Freund's Adjuvant
Knee Joint diagnostic imaging
Knee Joint drug effects
Knee Joint metabolism
Knee Joint pathology
Liposomes
Male
Mice, Inbred C57BL
Positron-Emission Tomography
Tomography, X-Ray Computed
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents chemistry
Anti-Inflammatory Agents therapeutic use
Arthritis, Experimental diagnostic imaging
Arthritis, Rheumatoid diagnostic imaging
Fluorodeoxyglucose F18 administration & dosage
Fluorodeoxyglucose F18 pharmacokinetics
Prednisolone administration & dosage
Prednisolone chemistry
Prednisolone therapeutic use
Radiopharmaceuticals administration & dosage
Radiopharmaceuticals pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 209
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 25902038
- Full Text :
- https://doi.org/10.1016/j.jconrel.2015.04.019