[(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 [(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.

• Authors: Tessa van der Geest, Josbert M Metselaar, Danny Gerrits, Peter L van Lent, Gert Storm, Peter Laverman, Otto C Boerman
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 209 Pg. 20-6 (Jul 10 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25902038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015. Published by Elsevier B.V.

Chemical References

• Adjuvants, Immunologic
• Anti-Inflammatory Agents
• Liposomes
• Radiopharmaceuticals
• Fluorodeoxyglucose F18
• Freund's Adjuvant
• Prednisolone

Topics

• Adjuvants, Immunologic
• Animals
• Anti-Inflammatory Agents (administration & dosage, chemistry, therapeutic use)
• Arthritis, Experimental (diagnostic imaging, drug therapy, metabolism, pathology)
• Arthritis, Rheumatoid (diagnostic imaging, drug therapy, metabolism, pathology)
• Bordetella pertussis
• Disease Progression
• Fluorodeoxyglucose F18 (administration & dosage, pharmacokinetics)
• Freund's Adjuvant
• Knee Joint (diagnostic imaging, drug effects, metabolism, pathology)
• Liposomes
• Male
• Mice, Inbred C57BL
• Positron-Emission Tomography
• Prednisolone (administration & dosage, chemistry, therapeutic use)
• Radiopharmaceuticals (administration & dosage, pharmacokinetics)
• Tomography, X-Ray Computed