11C-Acetate PET/CT Imaging As a Biomarker of Amyloid-Induced Neuroinflammation

Study Overview
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Brief Summary
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The proposed study aims to use 11C-acetate 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.

Official Title
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11C-Acetate PET/CT Imaging As a Biomarker of Amyloid-Induced Neuroinflammation

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Drug: 11C-acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for amnestic MCI cohort: Participants will be at least 65 years of age Positive brain amyloid PET/CT scan within 6 months of study screening Mini-mental status examination (MMSE) score ≥ 24 at screening visit 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 Participants must identify a study partner who is willing to accompany the patient to study visits 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: Participants will be at least 65 years of age History of negative brain amyloid PET/CT scan within 6 months of study screening OR negative CSF analysis for AD biomarkers within 6 months of study screening Mini-mental status examination (MMSE) > 27 at screening visit 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 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: Inability to tolerate or contraindication to imaging procedures (PET/CT or MRI) in the opinion of an investigator or treating physician History of stroke or other neurological disease that in the opinion of the investigator might interfere with evaluation of the 11C-Acetate scan Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amnestic MCI cohort<br>Patients with Mild Cognitive Impairment (MCI) (up to 14) will be recruited primarily from the Penn Memory Center (PMC). Clinical diagnostic criteria (described in further detail in Study Procedures section) will be used to identify subjects who are meet criteria for amnestic MCI. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. | Drug: 11C-acetate<br>* Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.<br>|
| Other: Control cohort<br>Normal control subjects in the same age range (up to 6) will be recruited from a current ongoing study investigating neuroinflammation in late life depression and healthy controls, from the control group in which all subjects receive MRI and LP and from the PMC research cohort. Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan. | Drug: 11C-acetate<br>* Participants will receive injection of radioactive tracer 11C-acetate and complete a PET/CT scan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate whether 11C-acetate uptake is increased in amyloid positive Mild Cognitive Impairment (MCI) subjects compared to amyloid negative healthy controls |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate 11C-acetate uptake to areas of greater amyloid plaque burden quantified on Amyloid PET/CT |  | 7 days | 
| Compare 11C-acetate in areas of mildly elevated PET SUVR to areas with high or sub-threshold amyloid burden |  | 7 days | 
| Correlate 11C-acetate uptake to levels of inflammatory markers in CSF |  | 7 days |