Effect of Alemtuzumab on Microglial Activation Positron Emission Tomography (PET) in Multiple Sclerosis

I. Subject Selection Subjects will be recruited at the Partners MS Center, 60 Fenwood Road, Boston, MA. In addition, referrals for the study will be obtained from MS Center at University of Massachusetts Medical center, Worcester, MA. Subjects will also be recruited through Health and Clinical Research OnCall websites, and from individual physician references. II. Study Procedures Initial Visit: During the first visit, subjects will be adminsitered a screening questionnaire. Subjects will review and eventually sign the consent form. They will be administered standardized questionnaires for cognitive testing and/or other co-morbidities. In addition, a blood sample will be drawn for genotype testing to identify high affinity, medium affinity and low affinity binders. Genotype Testing Blood sample drawn on the initial screening visit will be used to obtain genomic DNA for genotyping for polymorphism within the TSPO gene on chromosome 22q13.2, using a Taqman assay. High affinity and medium affinity binders will be included in the study while the low affinity binders will be excluded from the study. The blood sample will also be assessed for serum creatinine and estimated GFR because these subjects would need to undergo intravenous gadolinium contrast administration with their 3T MRIs. Blood samples will be stored for future immunophenotyping and/or other blood assays in the future. PET Visits: During the PET scan visits, all women subjects of child bearing age will undergo a stat quantitative serum hCG pregnancy test and only women with a negative test will undergo the radiopharmaceutical injection. PET imaging procedures PET scanning session will be at BWH PET scanning facility, 75 Francis Street, Boston, MA. For PET scanning, an intravenous (IV) catheter will be inserted into the radial antecubital or other arm or hand vein for injection of tracer. Radiopharmaceutical will be injected as a bolus (approximately 4mCi for \[F-18\]PBR06) followed by 5 mL of saline. At the time of imaging, the subjects will be positioned in the gantry of a PET camera. Head alignment will be made, relative to the canthomeatal line, using projected laser lines whose positions are known with respect to the slice positions of the scanner. A head support apparatus will be used to minimize head motion. Brain PET data acquisition will begin at the moment of radiotracer injection. Images will be acquired using a high-resolution PET/CT scanner. MRI Visit(s): All subjects will undergo a 3T Brain MRI during an MRI visit that may precede or follow the PET scan visit(s) but will be perfromed within 2 weeks of each other. MRI imaging procedures MRI scanning session will be performed at BWH MRI facility at 60 Fenwood Road, Boston, MA. MRIs will be performed with and without intravenous gadolinium-based contrast. Imaging Data The following data will be collected on all subjects during scanning sessions: During PET scanning, brain images will be acquired in 3-D mode, and dynamic acquisition scans will continue for 120 minutes. A non-diagnostic CT scan will be performed for attenuation correction of PET transmission data at the time of initiation of scanning. MRI data will be acquired as described above. T2/ FLAIR and other MRI images will be coregistered with PET images . Non Imaging/Clinical Data The following non-imaging/clinical data will be obtained: Expanded Disability Status Scale (EDSS) Timed 25-feet walk (T25W) MS Functional Composite (MSFC) Minimal Assessment of Cognitive Function Scale in MS (MACFIMS) battery Symbol digit modalities test (SDMT) MSQOL-54 scale (QOL) Modified fatigue Impact Scale (MFIS) Pittsburgh Sleep Quality Index (PSQI) Beck's Depression Inventory (BDI) Center for Epidemiological Studies-Depression Scale (CES-D) Hospital Anxiety and Depression Scale (HADS)