Evaluation of [11C]ZTP-1 to Image PDE4B

• INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet the following criteria:

• Aged 18 years or older.
• Must have undergone a screening assessment under protocol 01M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants or protocol 17M0181 Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies."
• Be healthy based on medical history, physical examination, and laboratory testing.
• Able to provide informed consent.
• Willingness to complete all study procedures including MRI tests.
• Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
• Agree to adhere to the lifestyle considerations

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

• Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
• History of neurologic illness or injury with the potential to affect study data interpretation.
• History of seizures, other than in childhood and related to fever.
• Recent exposure to radiation (i.e., PET from other research) that, when combined with this study, would be above the allowable limits.
• Inability to lie flat on camera bed for at least two hours, including claustrophobia and weight greater than the maximum for the scanner (500 lbs).
• HIV infection.
• Pregnancy or breastfeeding.
• Must not have substance use disorder or alcohol use disorder.
• Unable to travel to the NIH.
• Unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye.
• Known hypersensitivity to phosphodiesterase-4 (PDE-4) inhibitors (e.g. apremilast, roflumilast, nerandomilast, crisborole).
• Taking CYP3A4 inhibitors (e.g. grapefruit juice, clarithromycin, erythromycin, ritonavir); CYP3A4 inducers (e.g. phenobarbital St. John's Wort, rifampicin) or oral contraceptives containing gestodene and ethinyl estradiol.

EXCLUSION OF CHILDREN

Inclusion of children is not appropriate, because this protocol has more than minimal risk from radiation exposure without the possibility of direct benefit.

EXCLUSION OF PREGNANT OR BREASTFEEDING WOMEN:

Pregnant women will be excluded because this protocol involves exposure to ionizing radiation. Lactating women will be excluded because radioisotopes may be excreted in milk. We will perform a pregnancy test at screening and prior to all procedures to ensure participants are not pregnant. The test must be negative in order to continue on the study. In addition to completing a negative urine pregnancy test, on the day of PET scanning prior to PET scan procedures, participants of childbearing potential will undergo a clinical pregnancy screening interview with a licensed independent practitioner to confirm lack of pregnancy.

EXCLUSION OF PARTICIPANTS WHO ARE HIV POSITIVE:

Persons with HIV infection are excluded because HIV infection itself may change cAMP signaling.