PET Brain Imaging in Multiple Sclerosis, Alzheimer's Disease, and Other Neurological and Neuropsychiatric Diseases

Four groups of subjects will be recruited: 1. Subjects meeting the definition for RRMS by the International Panel Criteria, who are active, as defined by at least one MS relapse in the past 12 months, or at least one gadolinium enhancing lesion on Magnetic Resonance Imaging (MRI) within 3 months of enrollment. 2. Subjects meeting the definition for SPMS by International Panel Criteria and who have demonstrated deterioration in Expanded Disability Status Scale (EDSS) score in last 1 year 3. Subjects meeting the definition for probable AD based on National Institute of Neurological and Communicable Diseases-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. In terms of severity of disease, we will select subjects with mild AD, as defined by Mini-Mental Status Examination (MMSE) score of 20-26. 4. Healthy Controls The study will be performed in two phases. In the early pilot phase, 8 subjects with RRMS will undergo both \[C-11\]PBR28 PET scan and \[F-18\]PBR06 PET scan. At the end of this phase, a formal interim analysis will be performed and if imaging characteristics of \[F-18\]PBR06 are found non-inferior to or better than \[C-11\]PBR28, rest of the study will be completed using \[F-18\]PBR06. All subjects will also undergo 3-Tesla (3T) MRI of the brain. The goal sample size is 30 subjects including 6 healthy controls, 8 subjects with relapsing remitting MS, 8 subjects with secondary progressive MS (SPMS), and 8 subjects with AD. Subjects will be recruited by the PI, one of the other co-investigators, or a staff member listed on the protocol at the Partners MS Center and the Behavioral Neurology Clinic of Brigham and Women's Hospital. Side Effects Monitoring: No side effects from the radiopharmaceuticals are expected. The dose of radiopharmaceutical being administered in this study is below that at which we would expect any effect, including physical dependence and addiction. Subjects will be exposed to a small amount of radiation. The radiotracer will be prepared in such a way as to ensure that it is sterile and pyrogen free, and its radiochemical purity (RCP) will be determined using Silica Gel-Instant Thin Layer Chromatography and/or high pressure liquid chromatography (HPLC). In addition, because both \[F-18\]PBR06 and \[C-11\]PBR28 are non-FDA approved radioligands, their use for this study will be reviewed by Radioactive Drugs Research Committee. Subject Safety: Subject monitoring during MRI and PET scans will be performed using a 2-way intercom system between the scanner operator and subject and by visual monitoring of the subject through the window into the scan room (the subject is visible to the operator at all times). Subjects will need to lie still in the PET camera for period of 120 min, and subjects may find it uncomfortable to remain still over this time. Therefore, as mentioned above, subjects will be given the opportunity to take a break for up to 20 minutes after 70 minutes of PET scanning, following which the last 30 minutes of scanning will be completed. A standard head-support device will be used to make the subjects comfortable during the scanning. If subjects find an intravenous catheter or duration of scanning too uncomfortable, they are free to withdraw from the study at any time. The MRI scans take place in a confined space that makes some people claustrophobic. Claustrophobic individuals will be excluded from the study. Also during the scan the subject will hear loud banging noises and will therefore wear ear plugs to reduce this noise. Recruitment Process: Physicians at the Partners MS Center and the Brigham and Women's Hospital (BWH) Behavioral Neurology clinic may present the study to a subject during a regular scheduled clinic visit. If the subject is interested in the study, a copy of the consent form will be given. At the time of the subject's initial screening visit, a licensed physician investigator will answer any questions the subject may have regarding the study and subsequently obtain informed consent. In accordance with NIH guidelines, efforts will be made to attain a mix of study participants, in terms of gender and racial/ethnic representation. Consent Process: Informed consent will be obtained from the subjects by a licensed physician investigator on the study protocol. If the investigator is a clinician from the MS Center or Behavioral Neurology clinic, they will not be allowed to obtain consent from their own patients. Existing MS Center or Behavioral Neurology clinic subjects may be sent a letter describing the study and a copy of the consent document. Interested subjects are directed to contact research staff via a telephone number provided in the letter inviting participation in the study to set up a screening visit. They will have the opportunity to discuss the study with research study staff prior to giving consent as outlined above. Subjects approached for participation in the study during a routine clinical visit will have the opportunity to participate in the study at that time or they may choose to return for participation at another time in the future. All subjects will be informed that they are free to withdraw consent from the study at any time without affecting the quality or type of care that they receive at BWH. Subjects will be informed that they may not qualify for the study if their genetic analysis reveals that they are low affinity binders for translocator protein (TSPO). Monitoring and Quality Assurance: During the study period, subjects will be followed by their clinical neurologists for adverse events and disease progression. If problems are reported to their physicians, they will receive care as is normally performed. In addition, the Principal Investigator (PI) will review all laboratory results of tests undergone by the subjects during the study period and help co-ordinate any necessary care with patient's primary providers.