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

• Published in: EJNMMI research 2019-05, Vol.9 (1), p.38-9, Article 38
• Main 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.
• Format: Article
• Language: English
• Subjects: [18F]GE-180; Animals; Anti-VLA-4; Binding; Cardiac Imaging; Change detection; EAE; Emission analysis; Encephalomyelitis; Fluorine isotopes; Imaging; In vivo methods and tests; Medical imaging; Medicine; Medicine & Public Health; Monoclonal antibodies; Multiple sclerosis; Nuclear Medicine; Oncology; Original Research; Orthopedics; Positron emission; Positron emission tomography; Radiology; Rodents; Tomography; TSPO
• ISSN: 2191-219X; 2191-219X
• DOI: 10.1186/s13550-019-0508-7

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 [ 18 F]GE-180 to detect changes in a chronic multiple sclerosis-like focal delayed-type hypersensitivity experimental autoimmune encephalomyelitis ( f DTH-EAE) rat model during and after anti-VLA-4 monoclonal antibody (mAb) treatment. Thirty days after lesion activation, f DTH-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 [ 18 F]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 [ 18 F]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 [ 18 F]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 f DTH-EAE model to better understand the rebound phenomenon.