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

Background:

PDE4B is a protein in cells that helps turn off certain chemical signals after they ve done their job. It controls inflammation, immune responses, and some brain signaling. Measuring PDE4B levels in the body can help doctors manage a disease or know if a treatment is working. Researchers want to find out if a new tracer (a radioactive substance injected during imaging scans) can help them measure PDE4B in people more effectively.

Objective:

To test a new tracer ([11C]ZTP-1) during imaging scans of the brain and body in healthy people.

Eligibility:

Healthy people aged 18 and older. They must have been screened under protocols 01M-0254 or 17M0181.

Design:

Participants will have either 1 or 2 clinic visits.

During their first visit, all participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Prior to the scan, they will have blood and urine tests and a test of their heart function. The study tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body.

Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. The visit will last up to about 8 hours.

Some participants will have a PET/CT scan of only their brain. They will also have a magnetic resonance imaging (MRI) scan of the brain. They may need to return for a second visit for the MRI scan.

Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: 11C-ZTP-1

Detailed Description

Study Description:

This study is intended to provide information on the novel [11C]ZTP-1 radioligand and its ability to localize and measure PDE4B in the brain and body of healthy volunteers.

Objectives:

Primary Objective: To study the brain uptake of [11C]ZTP-1 and perform kinetic modeling of [11C]ZTP-1 in healthy volunteers.

Secondary Objective: To study brain retest variability and reliability, biodistribution, and dosimetry of [11C]ZTP-1 in healthy volunteers.

Endpoint:

Primary Endpoint: PDE4B density measured as distribution volume (VT), derived from kinetic modeling of [11C]ZTP-1 in the brain.

Secondary Endpoint: PDE4B density measured as distribution volume (VT) , evaluated in terms of test retest variability (absolute variability) and reliability (intraclass correlation coefficient [ICC]). Whole-body biodistribution and radiation burden, measured as Effective Dose (ED).)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Robert B Innis, M.D.; Phone Number: (301) 594-1368; Email: robert.innis@nih.gov
• Study Contact Backup: Name: Tara N Turon, C.R.N.P.; Phone Number: (301) 827-6599; Email: tara.turon@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: NIH Clinical Center Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: One-arm; All subjects will receive the same tests.	Drug: 11C-ZTP-1; Injected IV followed by PET scanning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Volume of Distribution	Quantification of 11C-ZPT-1	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosimetry, ICC, aTRV, and biodistribution.	Quantification of 11C-ZPT-1	120 minutes

Collaborators and Investigators

• Sponsor: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Robert B Innis, M.D., National Institute of Mental Health (NIMH)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Estimated): June 21, 2026
• Primary Completion (Estimated): March 19, 2029
• Study Completion (Estimated): October 3, 2030

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 2, 2026

More Information

Terms related to this study

• Keywords: PET Imaging; 11C-ZTP-1
• Other Study ID Numbers: 10002536; 002536-M

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The results will be submitted to ClinicalTrials.gov
• IPD Sharing Time Frame: 18 months after closure of protocol.
• IPD Sharing Access Criteria: BTRIS
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No