11C-Acetate PET/CT Imaging As a Biomarker of Amyloid-Induced Neuroinflammation
Condition: Mild Cognitive Impairment
MeSH terms: Neuroinflammatory Diseases; Cognitive Dysfunction
Intervention: 11C-acetate
Intervention description: Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No

Summary:

      The proposed study aims to use 11C-acetate position emission tomography/computed tomography
      (PET/CT) to preliminarily test and validate methods for imaging astrocyte activation as an
      early indicator of neuroinflammation in Alzheimer's disease (AD). 11C-Acetate PET/CT has been
      shown to quantify astrocyte activation in vivo, but no reports have evaluated its potential
      in AD. The investigators propose to test 11C-Acetate PET/CT as a marker for astrocyte
      activation associated with pathologic amyloid deposition in AD. The investigators will
      compare binding between subjects with early stage AD and healthy controls. Further, the
      investigators will investigate the correlation between amyloid and acetate binding. If the
      investigators find increased astrocyte activation in response to cerebral amyloid by showing
      a group difference in brain acetate uptake between disease and controls or a strong
      correlation between acetate and amyloid PET/CT binding. Validating neuroinflammation markers
      in AD ultimately may guide therapeutic modulation of beneficial and damaging
      neuroinflammation to slow disease progression, as well as providing new insights into AD
      pathophysiology.
    

Eligibility criteria:

        Inclusion Criteria for amnestic MCI cohort:

          1. Participants will be at least 65 years of age

          2. Positive brain amyloid PET/CT scan within 6 months of study screening

          3. Mini-mental status examination (MMSE) score ≥ 24 at screening visit

          4. A brain MRI is required. If a brain MRI has been performed within 6 months of
             11C-Acetate PET/CT and of adequate quality that scan may be used for the study
             analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of
             this study

          5. Participants must identify a study partner who is willing to accompany the patient to
             study visits

          6. Participants must be informed of the investigational nature of this study and provide
             written informed consent in accordance with institutional and federal guidelines prior
             to study-specific procedures. If the patient is unable to provide informed consent,
             the patient's legal representative may consent on behalf of the patient but the
             patient will be asked to confirm assent.

        Inclusion Criteria for Control cohort:

          1. Participants will be at least 65 years of age

          2. History of negative brain amyloid PET/CT scan within 6 months of study screening OR
             negative cerebrospinal fluid (CSF) analysis for AD biomarkers within 6 months of study
             screening

          3. Mini-mental status examination (MMSE) > 27 at screening visit

          4. A brain MRI is required. If a brain MRI has been performed within 6 months of
             enrollment to this study and of adequate quality that scan may be used for the study
             analysis, subjects who do not have a brain MRI will undergo a brain MRI as a part of
             this study

          5. Participants must be informed of the investigational nature of this study and provide
             written informed consent in accordance with institutional and federal guidelines prior
             to study-specific procedures.

        Exclusion Criteria for both cohorts:

          1. Inability to tolerate or contraindication to imaging procedures (PET/CT or MRI) in the
             opinion of an investigator or treating physician

          2. History of stroke or other neurological disease that in the opinion of the
             investigator might interfere with evaluation of the 11C-Acetate scan

          3. Any medical or psychological conditions that, in the opinion of the investigator,
             would compromise the subject's safety or successful participation in the study.