Probing Estrogen Sulfotransferase-Mediated Inflammation with [11C]-PiB in the Living Human Brain.

ABSTRACT

BACKGROUND: 2-(4'- [11C]Methylaminophenyl)-6-hydroxybenzothiazole ([11C]-PiB), purportedly a specific imaging agent for cerebral amyloid-ß plaques, is a specific, high affinity substrate for estrogen sulfotransferase (SULT1E1), an enzyme that regulates estrogen homeostasis. OBJECTIVE: In this work, we use positron emission tomography (PET) imaging with [11C]-PiB to assess the functional activity of SULT1E1 in the brain of moyamoya disease patients. METHODS: Ten moyamoya subjects and five control patients were evaluated with [11C]-PiB PET and structural MRI scans. Additionally, a patient with relapsing-remitting multiple sclerosis (RRMS) received [11C]-PiB PET scans before and after steroidal and immunomodulatory therapy. Parametric PET images were established to assess SULT1E1 distribution in the inflamed brain tissue. RESULTS: Increased [11C]-PiB SRTM DVR in the thalamus, pons, corona radiata, and internal capsule of moyamoya cohort subjects was observed in comparison with controls (p ≤ 0.01). This was observed in patients without treatment, with collateralization, and also after radiation. The post-treatment [11C]-PiB PET scan in one RRMS patient also revealed substantially reduced subcortical brain inflammation. In validation studies, [11C]-PiB autoradiography signal in the peri-infarct area of the rat middle cerebral arterial occlusion stroke model was shown to correlate with SULT1E1 immunohistochemistry. CONCLUSION: Strong [11C]-PiB PET signal associated with intracranial inflammation in the moyamoya syndrome cohort and a single RRMS patient appears consistent with functional imaging of SULT1E1 activity in the human brain. This preliminary work offers substantial and direct evidence that significant [11C]-PiB PET focal signals can be obtained from the living human brain with intracranial inflammation, signals not attributable to amyloid-ß plaques.