Assessment of 11C-JMJ-129 for Imaging PDE4D in Brain and Whole Body of Healthy Volunteers

Study Description:

This study is intended to provide information on the novel 11C-JMJ-129 radioligand and its ability to localize and measure PDE4D in the brain and body of healthy individuals.

Objectives:

Primary Objective: To study the brain uptake of 11C-JMJ-129 and perform kinetic modeling of the 11C-JMJ-129 in healthy individuals.

Secondary Objectives: To study brain retest variability and reliability, biodistribution, and dosimetry of 11C-JMJ-129 in healthy volunteers.

Endpoint:

Primary Endpoint: For both objectives, the primary endpoint is receptor density measured as distribution volume (VT).

Secondary Endpoint: Radiation burden to organs of the body.

• INCLUSION CRITERIA:
• Aged 18 years or older.
• Participants must have undergone a screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants."
• Healthy based on medical history, physical examination, and laboratory testing.
• Able to provide informed consent.
• Willing and able 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).
• Any current Axis I diagnosis.
• 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) which 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 breast feeding.
• Participants must not have substance use disorder or alcohol use disorder.
• Unable to travel to the NIH.
• Are 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.

Additional exclusions for participants receiving disulfiram:

Participants will be excluded if any of the following apply:

• Current use of, or use within the past 14 days, of metronidazole or paraldehyde.
• Consumption of alcohol or alcohol-containing products within 24 hours prior to disulfiram administration, or inability/unwillingness to abstain from alcohol containing products for 14 days after administration.
• History or presence of severe myocardial disease or coronary occlusion. Current or past history of psychotic disorders.
• Known hypersensitivity to disulfiram or other thiuram derivatives.