[18F]F-AraG PET Imaging in Alzheimer's Disease

Alzheimer's disease (AD) is known to involve neuroinflammation, but the role of T cell-mediated adaptive immunity remains poorly understood. This study uses [18F]F-AraG, a PET tracer that preferentially accumulates in activated T cells, to noninvasively assess immune-metabolic activity in the brain and peripheral organs in patients with AD.

Participants will undergo high-sensitivity total-body dynamic PET imaging using the uEXPLORER system. Intracerebral and systemic immune-metabolic activity will be assessed by analyzing total body [18F]F-AraG biodistribution and kinetics. .

The study will compare imaging metrics between AD participants and healthy controls.

Inclusion criteria

• Age ≥ 55 years
• Prior volumetric brain MRI available. If the prior MRI scan is not acquired within 6 months of [18F]F-AraG imaging or if the investigator determines that prior MRI scan cannot be used, a new MRI scan will be acquired.
• Able to tolerate a PET scan, and willingness and ability to comply with all protocol required procedures.
• For participants of reproductive potential - defined as individuals who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months), or who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy - willingness to use effective double barrier contraceptive methods (excluding withdrawal or timing methods) up to 1 day after the administration of [18F]F-AraG
• Subjects with possible or probable AD based on the NIA-Alzheimer's Association working group's diagnostic guidelines for AD.
• Have a study partner who has significant interaction with the subject and can report on the subject's activities of daily living.

Exclusion criteria

• Clinically significant psychiatric disease other than depression.
• Structural brain abnormalities on MRI (e.g. large infarct or mass) likely to interfere with interpretation of a PET scan.
• History of significant alcohol or substance abuse/dependence within the past 5 years.
• Non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the PET imaging session.
• Current or recent investigational drug use, defined as receiving any investigational medications or participation in another investigational drug trial within the last 30 days.
• Serious comorbidities (malignant and nonmalignant disease or other conditions) that in the opinion of the investigator could compromise study objectives.
• Conditions affecting immune function or conditions caused by immune system malfunction that could interfere with imaging, including known inflammatory or immune disorders, systemic malignancy, or chronic viral infections.
• Pregnant or nursing individuals. All participants of reproductive potential will undergo a urine or HCG serum pregnancy test with a sensitivity of at least 25 mIU/mL at screening and on the day of PET/CT imaging.
• Prior allogeneic stem cell or solid organ transplant.
• Previously diagnosed myelodysplasia syndrome or history of lymphoproliferative disease prior to study entry.
• Active systemic autoimmune diseases.
• Self-reported history of dysphoria or anxiety in closed spaces (i.e., uncontrolled claustrophobia).
• Concurrent or prior enrollment in a separate research study involving a PET scan performed within the last 12 months for research purposes only.
• Body weight is more than 240 kg (529 pounds)
• Recent use of medications containing guanosine or cysteine analogs.
• Any other criteria which would make the participant unsuitable for study participation, as determined by the Principal Investigator.