Microglial Activation Positron Emission Tomography (PET) Brain Imaging in Multiple Sclerosis and Alzheimer's Disease

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.

Inclusion Criteria:

1. Male and female subjects age 18 to 60 years. For Alzheimer's Disease patients, the age
range is going to be 18 to 70 years.

2. For RRMS, it needs to be active, which is defined as at least one relapse in the past
12 months or at least one gadolinium enhancing lesion on MRI within 3 months of
enrollment.

3. For SPMS, deterioration in EDSS score in the last year is required.

4. AD subjects with MMSE score of 20-26.

5. Subjects willing to undergo PET and MRI imaging

6. Subjects willing and able to give informed consent

Exclusion Criteria:

1. Individuals with a known alternate neurologic disorder, previous head injury, or
substance abuse.

2. Individuals with bipolar disease and schizophrenia

3. Concurrent medical conditions that contraindicate study procedures.

4. Women who are pregnant or nursing. Also, any woman who is seeking to become pregnant
or suspects she is pregnant will be excluded from enrollment.

5. Claustrophobia

6. Non-MRI compatible implanted devices

7. Corticosteroid treatment in the past four weeks

8. Low affinity binders (please see below)