Increased Microglial Activation in the Brain of Secondary Progressive Multiple Sclerosis Patients Detected Using [11C]PK11195 PET (S21.003)

Abstract

Objective: To investigate, whether microglial activation is increased in the brain of secondary progressive multiple sclerosis patients (SPMS) compared to healthy controls using [11C]PK11195 and positron emission tomography (PET). Background In SPMS, the widespread inflammation and neurodegeneration of the central nervous system leads to progressive disability. Neuropathological studies have shown that normal appearing white (NAWM) and gray matter (NAGM) are important loci of neuronal damage and microglial activation in progressive MS. However, these findings are poorly detectable using conventional imaging modalities (MRI). Importantly, in vivo imaging of activated microglia is possible using PET and translocator protein (TSPO) binding tracer [11C]PK11195. Design/Methods: Brain MRI and 60 minute dynamic [11C]PK11195 PET imaging were performed in 8 healthy controls (6 women, 2 men; mean age 49.8 years) and 9 SPMS patients (6 women, 3 men; mean age 49.6 years) without immunomodulatory treatment and with mean expanded disability status scale (EDSS) score 6.3. Anatomical regions of interests (ROI) were drawn onto the PET images co-registered with MRI. The ROI specific binding potential (BPnd) of [11C]PK11195 was calculated from the distribution volume ratio estimated using the Logan graphical analysis method with supervised cluster analysis (SVCA) approach. Results: The BPnd of [11C]PK11195 was significantly increased in the NAWM and thalami in SPMS patients compared to control group (p=0.008 and p=0.018, respectively). Also, a trend for increased BPnd in cortical gray matter of SPMS vs. control group was noted with a borderline significant difference in BP in the combined neocortex ROI (p=0.048). Conclusions: Evaluating microglial activation with a TSPO-binding PET-ligand provides a unique tool to assess diffuse brain inflammation in NAWM and NAGM areas in vivo. Our findings of increased [11C]PK11195 binding in NAWM and NAGM of SPMS patients underline the significance of diffuse microglial activation in progressive MS. Supported by: The Finnish Academy. Disclosure: Dr. Rissanen has received research support from Novartis. Dr. Tuisku has nothing to disclose. Dr. Virta has received research support from Orion-Pharma, GE Healthcare, and Bayer Schering. Dr. Paavilainen has nothing to disclose. Dr. Parkkola has nothing to disclose. Dr. Rinne has nothing to disclose. Dr. Airas has nothing to disclose.