Abstract Details

Title Cortical Microglial Activation on [F-18]PBR06-PET Predicts Progression Independent of Relapse Activity (PIRA) in Multiple Sclerosis: A 4.5-year Longitudinal Study

Topic Multiple Sclerosis

Presentation(s) S33 - Multiple Sclerosis: Biomarkers in MS (4:30 PM-4:42 PM)

Poster/Presentation
Number 006

Background

Microglial-activation may play a role in disease progression in MS. [F-18]PBR06-PET targeting 18-kDa-translocator-protein (TSPO) can detect abnormal microglial activation (MA) in MS.

Objective

The objectives of this study are to determine the ability of [F-18]PBR06-PET to predict progression independent of disease activity (PIRA) in multiple sclerosis (MS) and compare it with clinical measures, MRI volumetrics, and serum biomarkers .

Design/Methods

Twenty-two MS patients (mean age, 46±13 years; 16 females) who underwent [F-18]PBR06-PET scans were prospectively followed-up for an average duration of 4.5-years. PIRA was defined as at-least 0.5- and 1.0-point increase in EDSS in subjects with EDSS>/=5 and <5, respectively, without associated clinical-relapse or MRI-activity. Logarithmically transformed “glial activity load on PET” scores (calculated as the sum of voxel-by-voxel z-scores ≥4), “lnGALP,” were compared between progressors (PIRA) versus non-progressors (NP), and compared with differences in clinical measures, serum biomarkers, and total cortical thickness (CoT) between groups. Multivariate regression and receiver-operating-characteristic (ROC) analyses were performed.

Results

Cortical gray-matter (CoGM) lnGALP was higher and CoT was lower in PIRA versus NP (11.27±1.1 vs. 9.43±1.38, +19.5%, p = 0.009, and 2.44±0.08 vs. 2.51±0.07, -2.7%, p=0.03). On multivariate regression, CoGM-lnGALP was predictive of PIRA independent of CoT, age, EDSS, fatigue scores, disease-modifying treatment (DMT) and TSPO-binding-status (p<0.05). On ROC analysis, the AUC was 0.854 and 0.75 for PET and CoT, respectively (Youden’s-index (YI) 0.69 and 0.52). A CoGM-lnGALP cut-off value of >9.94 predicted PIRA with 100% sensitivity and 68.7% specificity that improved to 100% sensitivity and 100% specificity in a subgroup of patients treated with high-efficacy DMTs (n=13, YI=1, p<0.001). Serum neurofilament light chain and glial-fibrillary acid protein levels, brain and thalamic volume, and white matter lnGALP were not significantly different between groups.

Conclusions

Cortical microglial-activation on [F-18]PBR06-PET independently predicts PIRA in MS. Larger, prospective, longitudinal studies of [F-18]PBR06-PET in MS and PIRA are urgently warranted.

Authors/Disclosures
Tarun Singhal, MD (Brigham And Women's Hospital) PRESENTER	Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Singhal has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme Sanofi. Dr. Singhal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana LifeSciences. The institution of Dr. Singhal has received research support from Novartis. The institution of Dr. Singhal has received research support from Department of Defense. The institution of Dr. Singhal has received research support from Foundation for Neurologic Diseases.
Steven Cicero, BS (Brigham and Women's Hospital)	Steven Cicero has nothing to disclose.
Caleb Hansel	Mr. Hansel has nothing to disclose.
Shipra Dubey	Shipra Dubey has nothing to disclose.
Kyle Sullivan, Nuclear Medicine Technologist	Mr. Sullivan has nothing to disclose.
Nicolas Horan	Mr. Horan has nothing to disclose.
SHRISHTI SAXENA, MS	Miss SAXENA has nothing to disclose.
Renxin Chu (Brigham & Women's Hospital)	Dr. Chu has nothing to disclose.
Bonnie Glanz (Brigham and Women'S Hospital)	The institution of Ms. Glanz has received research support from CMSC. The institution of Ms. Glanz has received research support from NIH.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Siemens. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Rohit Bakshi, MD, FAAN	Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Bakshi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. The institution of Dr. Bakshi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Neuroimaging. The institution of Dr. Bakshi has received research support from Bristol Myers Squibb. The institution of Dr. Bakshi has received research support from EMD Serono. The institution of Dr. Bakshi has received research support from Novartis.
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

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