PET Imaging of Noradrenergic Transmission in the Brain

Study Description:

This study is intended to provide information on the novel 11C-ARMI radioligand and its ability to localize and measure Alpha-1A Adrenoreceptor (alpha-1A AR) in the brain and body of healthy volunteers.

Objectives:

Primary Objective:

To study the brain uptake of 11C-ARMI and perform kinetic modeling of 11C-ARMI in healthy volunteers.

Secondary Objectives:

To study brain retest variability and reliability, biodistribution, and dosimetry of 11C-ARMI 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 the body and expressed as Effective Dose (ED).

• INCLUSION CRITERIA:

• Aged 18 years or older.
• Must have undergone a screening assessment under protocol 01-M-0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants or 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 understand and willingness 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).
• 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.
• Taking medications reported to have significant binding to alpha-1 adrenoceptors, medications that that alter norepinephrine release, or medications that lower blood pressure including antihypertensives, diuretics, or phosphodiesterase-5(PDE-5) inhibitors (e.g. sildenafil, tadalafil, vardenafil) within five elimination halflives prior to any [11C]ARMI PET scan.
• Known hypersensitivity to quinazoline-class medications (e.g., prazosin), defined as any prior allergic or clinically significant adverse reaction requiring discontinuation or medical evaluation.
• Blood donation within 8 weeks (2 months) before study participation, or unwillingness to avoid blood donation for 8 weeks (2 months) after the study.