Introduction: Cladribine is an immune reconstitution-inducing treatment originally developed for hairy cell leukaemia. The oral form of cladribine is approved as a treatment for relapsing-remitting multiple sclerosis (RRMS). Cladribine depletes lymphocytes in the periphery, but based on in vitro studies, it may also affect CNS cell phenotypes such as microglial activation. Microglial activation can be measured in vivo using positron-emission tomography (PET) and 18 kDa translocator protein (TSPO)-binding radioligands, such as the [C-11]PK11195.

Objectives/Aims: To assess the effect of cladribine treatment on microglial activation in patients with RRMS.

Methods: The study cohort consisted of 14 patients with RRMS and 14 age- and sex-matched healthy controls. RRMS patients underwent clinical evaluation, MRI, and PET using [C-11]PK11195 radioligand immediately before commencement of cladribine treatment and after 18 months of treatment. The specific TSPO binding was evaluated using distribution volume ratio (DVR). Normal-appearing white matter (NAWM), thalamus and the 0–6 mm perilesional area were of special interest when performing the DVR estimations.

Results: The median (95% confidence interval) age of the patients with RRMS was 40.4 (36.0–43.2) years, the disease duration was 7.6 (5.4–16.0) years and EDSS was 2.5 (2.01–3.28) at baseline. The median age of the healthy controls was 42.5 (35.2–43.7) years. There were no discernible differences between the patients with RRMS and the healthy controls in the NAWM [C-11]PK11195 DVR (p = 0.54) or the thalamus [C-11]PK11195 DVR (p = 0.43) at baseline. EDSS scores did not change during the study (p = 0.47) and similarly, the DVRs remained stable in the NAWM (p = 0.10), in the thalamus (p = 0.67) and in the perilesional area (p = 0.29).

Conclusion: The TSPO-binding in the studied RRMS cohort was comparable to that of healthy controls at baseline and hence a reduction in TSPO-binding following treatment could not be expected in this cohort. [C-11]PK11195 DVR remained stable for the duration of the study.