[11C]PK11195-PET to assess neuroinflammation in multiple sclerosis (MS) patients undergoing an anti-inflammatory therapy

Objectives In MS, microglia and macrophages have a role in clearing myelin debris. However, a prolonged presence of these cells may contribute to further tissue injury. [C11]-PK11195 (PK) is a Positron Emission Tomography (PET) radioligand known to bind to the translocator protein expressed by activated microglia and macrophages. Therefore, once quantified, it may be effective in the assessment of disease progression. In the current study we used PK-PET imaging to assess the neuroinflammatory burden in MS patients receiving the anti-inflammatory drug Natalizumab (Tysabri). Our objective was to determine the effect of the drug at 3 and 6 months of treatment.

Methods Dynamic brain PK-PET images were acquired for 60 minutes. Quantification of PK uptake was done by volume of distribution (VT) calculation using image-derived input function. Input functions were computed using the carotid artery facilitated by fine reconstruction of 3 seconds frames that allows capturing the peak in activity. Using a segmented MRI that included the caudate, putamen, cerebellum, gray and white matter, whole brain and lesion mask, we assessed and compared these regions for each patient at baseline, 3 and 6 months follow-up.

Results 8 patients underwent pre and post treatment scans. Another 10 are scheduled to complete the protocol within the next 5 months. While undergoing the drug treatment, half of the patients demonstrated a significant decrease in VT (>16%, P <0.001) in all regions. Moreover, among all the 8 patients, VT significantly decreased in 5% (P<0.05). This reduction in VT may indicate the drug effect on overall neuroinflammation and neuroinflammation severity which correlated with clinical outcome.

Conclusions These results suggest that PK-PET may be a useful tool to assess anti-inflammatory treatment in MS patients. Moreover, anti-inflammatory treatment may reduce neuroinflammation burden and improve clinical outcome for some patients.

Research Support Biogen Idec