TY - JOUR T1 - Evaluation of the effect of fingolimod treatment on microglial activation using serial PET imaging in multiple sclerosis JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.116.183020 SP - jnumed.116.183020 AU - Marcus Sucksdorff AU - Eero Rissanen AU - Jouni Tuisku AU - Salla Nuutinen AU - Teemu Paavilainen AU - Johanna Rokka AU - Juha Rinne AU - Laura Airas Y1 - 2017/03/01 UR - http://jnm.snmjournals.org/content/early/2017/03/22/jnumed.116.183020.abstract N2 - Traditionally, multiple sclerosis (MS) has been considered a white matter (WM) disease with focal inflammatory lesions. It is, however, becoming clear that significant pathology, such as microglial activation, also takes place outside the plaque areas, i.e. in areas of normal appearing white matter (NAWM) and gray matter (GM). Microglial activation can be detected in vivo using an 18 kDa translocator protein (TSPO) binding radioligands and positron emission tomography (PET). It is unknown whether fingolimod affects microglial activation in MS. The aim of this study was to investigate whether serial PET can be used to evaluate the effect of fingolimod treatment on microglial activation. Methods: Ten relapsing-remitting MS (RRMS) patients were studied using the TSPO radioligand 11C-(R)-PK11195. Imaging was performed at baseline and after 8 and 24 weeks of fingolimod treatment. Eight healthy individuals were imaged for comparison. Microglial activation was evaluated as distribution volume ratio (DVR) of 11C‐(R)-PK11195. Results: The patients had had MS for an average of 7.9 years (± 4.3, mean ± standard deviation (SD)), their total relapses averaged 4 ± 2.4, and their Expanded Disability Status Scale was 2.7 ± 0.5. The patients were switched to fingolimod due to safety reasons or therapy escalation. The mean washout period before the initiation of fingolimod was 2.3 ± 1.1 months. The patients were clinically stable on fingolimod. At baseline, microglial activation was significantly higher in the combined NAWM and GM areas of MS patients compared with healthy controls (P = 0.021). 11C‐(R)-PK11195 binding was reduced (−12.31%) within the combined T2 lesion area after six months of fingolimod treatment (P = 0.040), but not in the areas of NAWM or GM. Conclusion: Fingolimod treatment reduced microglial/macrophage activation at the site of focal inflammatory lesions, presumably by preventing leukocyte trafficking from the periphery. It did not affect the widespread, diffuse microglial activation in the NAWM and GM. The study opens new vistas for designing future therapeutic studies in MS that use the evaluation of microglial activation as an imaging outcome measure. ER -