Background: Aging-related progressive neurological disorders include frontotemporal dementia, Lou Gehrig s disease, and Alzheimer s disease. Little is known about what causes these disorders. Brain inflammation may be involved. Researchers want to see if scans using radioactive drugs can show brain inflammation. Objective: To see if the drug \[11C\]ER176 can show inflammation in the brain in people with certain progressive neurological disorders compared to healthy adults. Also to find genes that might be associated with or cause these disorders. Eligibility: People ages 18 and older with an aging-related neurological disorder, and healthy adults Design: Participants will be screened with a medical history, physical exam, neurological exam, psychiatric history, and blood tests. Participants will have 2-5 visits for the first session. They will have 2 PET scans and 1 MRI scan. They may have 3 more sessions: 6 months to about 18 months later, 1 year after that, and about 30 months to 5 years after the first visit. There may be up to 20 total visits. For the scans, participants will lie on a bed that slides into the scanners. For the PET scans, a strap will fix their head in place. A radioactive drug will be injected through a catheter. A needle will guide a thin plastic tube into an arm vein. Additional catheters may be put in place to draw blood. Each PET will take 2 hours. The MRI will take 30 60 minutes. At each session, participants will have a brief interview, medical history, physical exam, blood and urine tests, heart tests, and memory and thinking tests. They may donate blood for DNA tests.
Objectives The primary objective is to explore if human subjects with neurodegenerative diseases exhibit different level of neuroinflammation, as measured by brain uptake of a 3rd generation \[11C\]ER176 TSPO ligand, compared to control subjects. The secondary objectives are to determine, 1) if \[11C\]ER176 TSPO brain uptake shows disease-specific patterns across different neurodegenerative diseases and/or genetic mutations, and 2) if longitudinal imaging of individual patients shows a correlation between interval change of tracer uptake and disease progression. Study population Adults referred with a clinical diagnosis or with an increased risk of frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer s disease, other related adult-onset neurodegenerative disorders, or healthy control subjects. Design Participants will undergo a general and neurological exam, a standard battery of neuropsychological tests to measure cognitive function, blood tests for analysis of TSPO polymorphisms, MRI of the brain, and PET imaging with the \[11C\]ER176 TSPO radioligand and \[11C\]PIB amyloid radioligand. Participants will be invited to return for repeat evaluations approximately 1, 2, and 3-5 years after their initial evaluation. Outcome measures Brain PET and MRI scans will be co-registered for anatomic definition of regions of interest, and standard uptake value (SUV) will be calculated in various brain regions. \[11C\]ER176 PET data will be analyzed with compartmental modeling. \[11C\]PIB PET and MRI data will be adjunctly used for segregating the collected data by disease subtype. For the primary objective, we will compare TSPO radioligand uptake of healthy controls compared to subjects with neurodegenerative diseases. For secondary objectives, we will determine if neuroanatomical regions of tracer uptake differ across different neurodegenerative disease subtypes, and if interval change of tracer uptake correlates with disease progression in longitudinal imaging of individual subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
13
PET biomarker for inflammation
PET biomarker for amyloid
Participants underwent PET scan with \[11C\]ER176 and/or 11C-PIB
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Standard Uptake Value Ratio Compared to the Cerebellum (SUVR) Area Under the Curve (AUC) (60-90min)
Participants underwent brain positron emission tomography (PET) scan with \[11C\]ER176 and standard uptake value (SUV) was measured over 90 minutes and divided by SUV of the cerebellum to determine difference of \[11C\]ER176 brain uptake
Time frame: Up to 90 minutes during scan
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