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- Title
Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation.
- Authors
Vainio, S. K.; Dickens, A. M.; Tuisku, J.; Eskola, O.; Solin, O.; Löyttyniemi, E.; Anthony, D. C.; Rinne, J. O.; Airas, L.; Haaparanta-Solin, M.
- Abstract
Background: Positron emission tomography (PET) can be used for in vivo evaluation of the pathology associated with multiple sclerosis. We investigated the use of longitudinal PET imaging and the 18-kDa translocator protein (TSPO) binding radioligand [18F]GE-180 to detect changes in a chronic multiple sclerosis-like focal delayed-type hypersensitivity experimental autoimmune encephalomyelitis (fDTH-EAE) rat model during and after anti-VLA-4 monoclonal antibody (mAb) treatment. Thirty days after lesion activation, fDTH-EAE rats were treated with the anti-VLA-4 mAb (n = 4) or a control mAb (n = 4; 5 mg/kg, every third day, subcutaneously) for 31 days. Animals were imaged with [18F]GE-180 on days 30, 44, 65, 86 and 142. Another group of animals (n = 4) was used for visualisation the microglia with Iba-1 at day 44 after a 2-week treatment period. Results: After a 2-week treatment period on day 44, there was a declining trend (p = 0.067) in [18F]GE-180-binding in the anti-VLA-4 mAb-treated animals versus controls. However, cessation of treatment for 4 days after a 31-day treatment period increased [18F]GE-180 binding in animals treated with anti-VLA-4 mAb compared to the control group (p = 0.0003). There was no difference between the groups in TSPO binding by day 142. Conclusions: These results demonstrated that cessation of anti-VLA-4 mAb treatment for 4 days caused a transient rebound increase in neuroinflammation. This highlights the usefulness of serial TSPO imaging in the fDTH-EAE model to better understand the rebound phenomenon.
- Subjects
TRANSLOCATOR proteins; SPRAGUE Dawley rats; MULTIPLE sclerosis; POSITRON emission tomography; THERAPEUTICS; RATS; MONOCLONAL antibodies
- Publication
EJNMMI Research, 2019, Vol 9, Issue 1, pN.PAG
- ISSN
2191-219X
- Publication type
Article
- DOI
10.1186/s13550-019-0508-7