Establishing 18F-PBR06 PET Imaging as a Viable Pharmacodynamic Endpoint in MSA

Sixteen subjects with a probable MSA diagnosis will be recruited for this study. A probable MSA diagnosis will be based on the following criteria:

• Autonomic failure involving urinary incontinence (inability to control the release of urine form the bladder, with erectile dysfunction in males) or an orthostatic decrease of blood pressure within 3 min of standing by at least 30 mmHg systolic or 15 mm Hg diastolic and
• Poorly levodopa-responsive Parkinsonism (bradykinesia with rigidity, tremor, or postural instability) or
• A cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction)

Summary:

Subjects will be recruited during routine clinical appointments by their physician or one of the other co-investigators listed on the protocol at the Movement Disorders Clinic, 60 Fenwood Road, Boston, MA. Once the subject gives the informed consent, investigators will be administering standardized questionnaires for assessment of disease severity, comorbidities and/or presence of symptoms, as applicable to a given cohort. In addition, a blood sample will be drawn for genotype testing to identify high affinity, medium affinity, and low affinity binders. Any subjects identified as low affinity binders will be excluded from the study.

Subjects will undergo two PET scans with [F-18]PBR06 at BWH PET scanning facility at 75 Francis Street, Boston, MA. For PET scanning, an intravenous (IV) catheter will be inserted for injection of tracer. In addition, prior to the tracer injection, a second IV catheter may be inserted into the other arm or hand vein on the contralateral side for blood sampling. To increase the usefulness of blood sampling for radiotracer analysis, the hand or arm used for blood sampling may be wrapped in an electrical warmer with the thermostat set at 44°C for approximately 5-10 minutes.The whole PET session will last approximately 120 min. At the time of imaging, the subjects will be positioned in the gantry of a PET camera. A head support will be used to minimize head motion.