First-in-Human Evaluation of an Astrocytic Glutamate Transporter (EAAT2) PET Tracer in Dementia

Inclusion Criteria:

1. Age 40-75
2. Age-suitable BMI
3. Ability to provide written informed consent and willingly comply with protocol requirements or has a legal authorized representative/guardian who provides surrogate informed consent.
4. No apparent physical disorder.
5. Radial, ulnar, or brachial artery suitable for catheterization.
6. Non-smoker, and not taking OTC nicotine cessation - to limit peripheral metabolism events.
7. Devoid of CNS prescription drugs for three weeks - to limit peripheral metabolism events.

   For Cohort 2B and 2C:
8. Must have a study partner (informant) who spends a minimum average of 5 hours per week with the participant (e.g. family member, significant other, friend, caregiver), is generally aware of the participant's daily activities, can provide information about the participant's cognitive and functional performance, and will accompany the participant in all study procedure.
9. Recent (within 6 mo.) MME clinical scores.

Exclusion Criteria:

1. Unable to provide written informed consent and unwilling to comply with protocol requirements, or does not have a legal authorized representative/guardian who can provide surrogate informed consent.
2. Inadequate arterial access.
3. Receipt of radioisotope \< 5 half-lives within \[18F\]RP-115 imaging- as to not confound any scans with radiation background for previous scanning, and unsuitable organ dosimetry thresholds from previous (\> two weeks) PET scans.
4. The performed \[18F\]RP-115 scan(s) must not represent \> 3 PET studies total within one year.
5. Contra-indication to magnetic resonance, including permanent pacemaker, implantable metallic device, etc.; or severe claustrophobia.
6. Participants who are pregnant (female patients of childbearing age will be tested prior to injection of tracer- positive test excludes from the study)
7. Participants who are breast-feeding.
8. Have a medical condition or other circumstances that in the opinion of the project physicians would significantly decrease chances of obtaining reliable data, achieving the study objective or completing the study.