[18F]SF12051 for Imaging the 18-kDa Translocator Protein (TSPO) in Brain and Whole Body of Healthy Subjects

Phase 1

Terminated

Conditions: Healthy

Interventions: Drug: 18F-SF12051

Registration Number: NCT05564429

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary: Background:

Inflammation in the brain plays a role in many diseases. Being able to measure inflammation in a person's brain might help to diagnose and treat these diseases. One protein (TSPO) appears in higher numbers when inflammation affects the brain. To see TSPO when a person's body is scanned, researchers need a substance called a radiotracer that will attach to this protein and no other molecules.

Objective:

This study will test whether a new radiotracer (\[18F\]SF12051) can make TSPO appear on PET scans of a person's brain and body.

Eligibility:

Healthy people aged 18 and older.

Design:

This study requires 2 to 4 visits to the clinic.

All participants will be screened. They will have a physical exam. They will have blood tests and a test of their heart function.

Some participants will have a positron emission tomography (PET) scan of the whole body. The radiotracer will be injected through a tube (catheter) placed in a vein in the arm. The PET scanner is a machine shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. The scan will take about 2 hours.

Some participants will have a PET scan of just their head. After they are injected with the radiotracer, they will lie on a bed with their head in the scanner. Blood will be drawn from a catheter in the wrist during the scan.

Some participants will have a magnetic resonance imaging (MRI) scan of the brain. They will lie on a narrow bed that slides into a tube.

Detailed Description: Study Description:

This study is intended to provide information on the novel \[18F\]SF12051 radioligand and its ability to localize and measure TSPO in the brain and body of healthy individuals.

Objectives:

Primary Objective: To study the brain uptake of \[18F\]SF12051 and perform kinetic modeling of the \[18F\]SF12051 in the three different TSPO genotypes.

Secondary Objectives: To study the brain retest characteristics, biodistribution and dosimetry of \[18F\]SF12051 in healthy subjects.

Endpoints:

Primary Endpoint: The distribution volume of the radioligand and stability over time calculated with compartmental modeling, attention paid to differences in mean distribution volumes between TSPO genotypes for determining genotype sensitivity.

Secondary Endpoints: Retest variability and reliability and organ time- activity curves to determine biodistribution and dosimetry.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low affinity binder (LAB) Translocator Protein (TSPO) genotype	18F-SF12051	Healthy participants with LAB TSPO genotype receive 18F-SF12051 intravenously followed by whole body or brain positron emission tomography (PET) scan. Participants were randomized to either phase 1, 2, or 3. Phases 1 \& 3 had whole body PET scan and phase 2 had brain PET scan.
Mixed affinity binder (MAB) Translocator Protein (TSPO) genotype	18F-SF12051	Healthy participants with MAB TSPO genotype receive 18F-SF12051 intravenously followed by whole body or brain positron emission tomography (PET) scan. Participants were randomized to either phase 1, 2, or 3. Phases 1 \& 3 had whole body PET scan and phase 2 had brain PET scan.
High affinity binder (HAB) Translocator Protein (TSPO) genotype	18F-SF12051	Healthy participants with HAB TSPO genotype receive 18F-SF12051 intravenously followed by whole body or brain positron emission tomography (PET) scan. Participants were randomized to either phase 1, 2, or 3. Phases 1 \& 3 had whole body PET scan and phase 2 had brain PET scan.

Primary Outcome Measures

Name	Time	Method
Whole Body PET Uptake of [18F]SF12051 - Phase 1	Up to 120 minutes during the scan	Participant received whole body PET scan and Uptake of \[18F\]SF12051 was measured using the Siemens Biograph mCT. Organ dosimetry was measured as microsieverts per mega-becquerel (uSv/MBq).
Brain PET Uptake of [18F]SF12051 - Phase 2	Up to 120 minutes during the scan	Participant received brain PET scan and Uptake of \[18F\]SF12051 was measured using the Siemens Biograph mCT. Volume of distribution (Vt) was calculated via 2-Tissue-Compartment Model with plasma input function.
Whole Body PET Uptake of [18F]SF12051 - Phase 3	Up to 120 minutes during the scan	Participant received whole body PET scan and Uptake of \[18F\]SF12051 was measured using the Siemens Biograph mCT. Organ dosimetry was measured as microsieverts per mega-becquerel (uSv/MBq).

Secondary Outcome Measures

Name	Time	Method
Test-Retest Variability of [18F]SF12051	Up to 120 minutes during the scan	Assess test-retest variability of \[18F\]SF12051 using absolute test-retest variability (aTRV). aTRV = \\| retest value - test value\\| / (test value + retest value) \* 200%
Area Under the Organ Time-Activity Curves From 0-120 - Phase 1	Up to 120 minutes during the scan	Biodistribution and dosimetry of \[18F\]SF12051 in healthy subjects was measured as area under the curve from 0-120 minutes shown as concentration of radioactivity reported as standard uptake values (SUV) x time during the course of the scans for each organ.
Test-Retest Reliability of [18F]SF12051	Up to 120 minutes during the scan	Assess test-retest reliability of \[18F\]SF12051 using intraclass correlation coefficient (ICC) ICC = (between-subject standard deviation)\^2/\[(between-subject standard deviation)\^2 + (within-subject standard deviation)\^2\]
Area Under the Organ Time-Activity Curves From 0-120 - Phase 3	Up to 120 minutes during the scan	Biodistribution and dosimetry of \[18F\]SF12051 in healthy subjects was measured as area under the curve from 0-120 minutes shown as concentration of radioactivity reported as standard uptake values (SUV) x time during the course of the scans for each organ.