Healthy
Conditions
Keywords
PET Imaging, Neuroinflammation, Tspo
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.
Interventions
DRUG18F-SF12051
Injected intravenously followed by PET scanning
Sponsors
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all of the following criteria: * Aged 18 years or older. * Healthy based on medical history, physical examination, and laboratory testing. * Able to provide informed consent. * Willing and able to complete all study procedures. * Have been screened for TSPO genotype under 01-M-0254 The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants. * Have 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 * Does not apply to Phase 1 and 3 participants as they will not have an arterial line.
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; acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen); hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct); mineral panel (albumin, calcium, magnesium, phosphorus); prothrombin and partial prothrombin tests. * Participants should not have taken NSAIDs or willow bark tea for two weeks prior to the PET scan. * Any current Axis I diagnosis. * Positive test for HIV. * Unable to have an MRI scan\*. * 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). * Pregnancy or breast feeding. * Able to get pregnant but does not use birth control. * Participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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% |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Affinity Binder (HAB) Translocator Protein (TSPO) Genotype Healthy participants with HAB TSPO genotype receive 18F-SF12051 intravenously followed by whole body or brain positron emission tomography (PET) scan. | 4 |
| Low Affinity Binder (LAB) Translocator Protein (TSPO) Genotype Healthy participants with LAB TSPO genotype receive 18F-SF12051 intravenously followed by whole body or brain positron emission tomography (PET) scan. | 2 |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype Healthy participants with MAB TSPO genotype receive 18F-SF12051 intravenously followed by whole body or brain positron emission tomography (PET) scan. | 4 |
| Total | 10 |
Baseline characteristics
| Characteristic | High Affinity Binder (HAB) Translocator Protein (TSPO) Genotype | Low Affinity Binder (LAB) Translocator Protein (TSPO) Genotype | Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 4 participants | 2 participants | 4 participants | 10 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 | 0 / 4 |
| other Total, other adverse events | 1 / 4 | 0 / 2 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 | 0 / 4 |
Outcome results
Primary
Brain PET Uptake of [18F]SF12051 - Phase 2
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.
Time frame: Up to 120 minutes during the scan
Population: All participants who completed phase 2 of the study. Data for one participant was not useable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Brain PET Uptake of [18F]SF12051 - Phase 2 | 0.833333333 mL*cm-3 | Standard Deviation 0.328 |
| Low Affinity Binder (LAB) Translocator Protein (TSPO) Genotype | Brain PET Uptake of [18F]SF12051 - Phase 2 | 0.40 mL*cm-3 | Standard Deviation 0.0225 |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Brain PET Uptake of [18F]SF12051 - Phase 2 | 0.90 mL*cm-3 | Standard Deviation 0.036 |
Primary
Whole Body PET Uptake of [18F]SF12051 - Phase 1
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).
Time frame: Up to 120 minutes during the scan
Population: Participant who completed phase 1 of the study. Whole body PET imaging was done for one subject with a low injection activity of \~2 mCi to confirm that no organ has prominently high uptake of \[18F\]SF12051.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Liver | 8 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Brain | 6 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Heart | 17 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Kidneys | 16 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Lungs | 11 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Stomach | 18 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Spleen | 15 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Bone Marrow | 15 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Gallbladder | 16 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Small intestine | 25 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Testicles | 14 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Urinary bladder | 21 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 1 | Whole body | 15 uSv/MBq |
Primary
Whole Body PET Uptake of [18F]SF12051 - Phase 3
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).
Time frame: Up to 120 minutes during the scan
Population: Participant who completed phase 3 of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Ovaries | 15 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Brain | 5 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Heart | 15 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Liver | 12 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Kidneys | 17 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Lungs | 13 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Stomach | 15 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Spleen | 10 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Bone Marrow | 12 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Gallbladder | 20 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Small intestine | 20 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Urinary bladder | 12 uSv/MBq |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Whole Body PET Uptake of [18F]SF12051 - Phase 3 | Whole body | 15 uSv/MBq |
Secondary
Area Under the Organ Time-Activity Curves From 0-120 - Phase 1
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.
Time frame: Up to 120 minutes during the scan
Population: Participant who completed phase 1 of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Brain | 84.78437744 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Heart | 497.9329916 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Liver | 357.8754055 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Kidneys | 345.5662222 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Lungs | 93.28630134 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Stomach | 348.3474892 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Spleen | 438.5340085 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Urinary bladder | 271.9311702 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Bone Marrow | 868.883177 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Gallbladder | 152.5233703 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Small intestine | 218.0137982 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 1 | Testicles | 71.86889245 SUV*minutes |
Secondary
Area Under the Organ Time-Activity Curves From 0-120 - Phase 3
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.
Time frame: Up to 120 minutes during the scan
Population: Participant who completed phase 3 of the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Brain | 56.6832231 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Heart | 491.710075 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Liver | 141.3314325 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Kidneys | 215.9146934 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Lungs | 92.14993947 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Stomach | 170.0881894 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Spleen | 238.9553087 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Urinary bladder | 234.1664917 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Bone Marrow | 230.539214 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Gallbladder | 115.1009919 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Small intestine | 144.9270488 SUV*minutes |
| Mixed Affinity Binder (MAB) Translocator Protein (TSPO) Genotype | Area Under the Organ Time-Activity Curves From 0-120 - Phase 3 | Ovaries | 67.67155656 SUV*minutes |
Secondary
Test-Retest Reliability of [18F]SF12051
Assess test-retest reliability of \[18F\]SF12051 using intraclass correlation coefficient (ICC) ICC = (between-subject standard deviation)\^2/\[(between-subject standard deviation)\^2 + (within-subject standard deviation)\^2\]
Time frame: Up to 120 minutes during the scan
Population: Data were not collected due to termination of the study
Secondary
Test-Retest Variability of [18F]SF12051
Assess test-retest variability of \[18F\]SF12051 using absolute test-retest variability (aTRV). aTRV = \| retest value - test value\| / (test value + retest value) \* 200%
Time frame: Up to 120 minutes during the scan
Population: Data were not collected due to termination of the study