Probing Estrogen Sulfotransferase-Mediated Inflammation with [11C]-PiB in the Living Human Brain
| Autor: | Jorge R. Barrio, Sung-Cheng Huang, Omid Mirfendereski, Koon-Pong Wong, Payam Mirfendereski, David S Liebeskind, Amy S. Yu, Andrew Surmak, John M. Ringman, Graham B. Cole, Alexander A Aabedi, Kenji Hirata |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty Internal capsule 03 medical and health sciences 0302 clinical medicine medicine Humans Carbon Radioisotopes Estrogen Sulfotransferase Moyamoya disease Stroke Aged Inflammation medicine.diagnostic_test business.industry General Neuroscience Multiple sclerosis Brain General Medicine Human brain Middle Aged medicine.disease Magnetic Resonance Imaging Functional imaging Psychiatry and Mental health Clinical Psychology 030104 developmental biology medicine.anatomical_structure Positron emission tomography Positron-Emission Tomography Female Moyamoya Disease Sulfotransferases Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 73:1023-1033 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Background 2-(4'- [11C]Methylaminophenyl)-6-hydroxybenzothiazole ([11C]-PiB), purportedly a specific imaging agent for cerebral amyloid-β 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-β plaques. |
| Databáze: | OpenAIRE |
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