Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation

A1 Journal article (refereed)

Internal Authors/Editors

Publication Details

List of Authors: S. K. Vainio, A. M. Dickens, J. Tuisku, O. Eskola, O. Solin, E. Löyttyniemi, D. C. Anthony, J. O. Rinne, L. Airas, M. Haaparanta-Solin
Publication year: 2019
Journal: EJNMMI Research
Journal acronym: EJNMMI RES
Volume number: 9
Number of pages: 9
ISSN: 2191-219X


BackgroundPositron 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 [F-18]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; 5mg/kg, every third day, subcutaneously) for 31days. Animals were imaged with [F-18]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.ResultsAfter a 2-week treatment period on day 44, there was a declining trend (p=0.067) in [F-18]GE-180-binding in the anti-VLA-4 mAb-treated animals versus controls. However, cessation of treatment for 4days after a 31-day treatment period increased [F-18]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.ConclusionsThese results demonstrated that cessation of anti-VLA-4 mAb treatment for 4days 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.


Anti-VLA-4, EAE, [F-18]GE-180, TSPO

Last updated on 2020-07-04 at 09:59