Evaluation of a Novel Positron Emission Tomography (PET Radiotracer for TARP Gamma-8
| Status: | Terminated |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 10/14/2018 |
| Start Date: | March 5, 2014 |
| End Date: | December 1, 2016 |
Objective
Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the
excitatory neurotransmission in the mammalian central nervous system (CNS). Based on
pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent
years it has become apparent that the receptors do not function alone, but in the company of
auxiliary proteins that regulate their activity [1]. Some of these have been shown to
modulate AMPA receptor trafficking, gating and pharmacology and are classified as
transmembrane AMPA receptor regulatory proteins, or TARPs ( >=-2, >=-3, >=-4, >=-5, >=-7, and
>=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy,
neuropathic pain, and bipolar disorder [1]. In a preclinical collaboration with Eli Lilly, we
developed a promising radioligand, 18F-TARP252 to image TARP >=-8 using positron emission
tomography (PET).
This protocol covers three phases:
- Phase 1: kinetic brain imaging to quantify TARP >=-8 in brain relative to concurrent
measurement of the parent radioligand in arterial plasma;
- Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the
radiation-absorbed doses by performing whole body imaging;
- Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the
parent radioligand in arterial plasma.
Study Population
Healthy adult female and male volunteers (n=22, ages 18 - 55) will undergo brain imaging. An
additional eight healthy volunteers will undergo whole body dosimetry analysis.
Design
For quantification of TARP >=-8, 22 healthy controls will have brain PET imaging using
18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional
subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will
be used.
Outcome Measures
To assess quantitation of TARP >=-8 with 18F-TARP252, we will primarily use two outcome
measures: the identifiability and time stability of distribution volume calculated with
compartmental modeling. In test-retest study, we will calculate the retest variability. We
will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to
organs and effective dose to the body.
Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the
excitatory neurotransmission in the mammalian central nervous system (CNS). Based on
pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent
years it has become apparent that the receptors do not function alone, but in the company of
auxiliary proteins that regulate their activity [1]. Some of these have been shown to
modulate AMPA receptor trafficking, gating and pharmacology and are classified as
transmembrane AMPA receptor regulatory proteins, or TARPs ( >=-2, >=-3, >=-4, >=-5, >=-7, and
>=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy,
neuropathic pain, and bipolar disorder [1]. In a preclinical collaboration with Eli Lilly, we
developed a promising radioligand, 18F-TARP252 to image TARP >=-8 using positron emission
tomography (PET).
This protocol covers three phases:
- Phase 1: kinetic brain imaging to quantify TARP >=-8 in brain relative to concurrent
measurement of the parent radioligand in arterial plasma;
- Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the
radiation-absorbed doses by performing whole body imaging;
- Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the
parent radioligand in arterial plasma.
Study Population
Healthy adult female and male volunteers (n=22, ages 18 - 55) will undergo brain imaging. An
additional eight healthy volunteers will undergo whole body dosimetry analysis.
Design
For quantification of TARP >=-8, 22 healthy controls will have brain PET imaging using
18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional
subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will
be used.
Outcome Measures
To assess quantitation of TARP >=-8 with 18F-TARP252, we will primarily use two outcome
measures: the identifiability and time stability of distribution volume calculated with
compartmental modeling. In test-retest study, we will calculate the retest variability. We
will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to
organs and effective dose to the body.
Objective
Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the
excitatory neurotransmission in the mammalian central nervous system (CNS). Based on
pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent
years it has become apparent that the receptors do not function alone, but in the company of
auxiliary proteins that regulate their activity [1]. Some of these have been shown to
modulate AMPA receptor trafficking, gating and pharmacology and are classified as
transmembrane AMPA receptor regulatory proteins, or TARPs ( >=-2, >=-3, >=-4, >=-5, >=-7, and
>=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy,
neuropathic pain, and bipolar disorder [1]. In a preclinical collaboration with Eli Lilly, we
developed a promising radioligand, 18F-TARP252 to image TARP >=-8 using positron emission
tomography (PET).
This protocol covers three phases:
- Phase 1: kinetic brain imaging to quantify TARP >=-8 in brain relative to concurrent
measurement of the parent radioligand in arterial plasma;
- Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the
radiation-absorbed doses by performing whole body imaging;
- Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the
parent radioligand in arterial plasma.
Study Population
Healthy adult female and male volunteers (n=22, ages 18 - 55) will undergo brain imaging. An
additional eight healthy volunteers will undergo whole body dosimetry analysis.
Design
For quantification of TARP >=-8, 22 healthy controls will have brain PET imaging using
18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional
subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will
be used.
Outcome Measures
To assess quantitation of TARP >=-8 with 18F-TARP252, we will primarily use two outcome
measures: the identifiability and time stability of distribution volume calculated with
compartmental modeling. In test-retest study, we will calculate the retest variability. We
will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to
organs and effective dose to the body.
Ionotropic glutamate receptors are ligand-gated ion channels responsible for most of the
excitatory neurotransmission in the mammalian central nervous system (CNS). Based on
pharmacology, they have been grouped into three subtypes-NMDA, AMPA and kainate. In recent
years it has become apparent that the receptors do not function alone, but in the company of
auxiliary proteins that regulate their activity [1]. Some of these have been shown to
modulate AMPA receptor trafficking, gating and pharmacology and are classified as
transmembrane AMPA receptor regulatory proteins, or TARPs ( >=-2, >=-3, >=-4, >=-5, >=-7, and
>=-8). Genetic data indicate a possible role of TARPs in schizophrenia, depression, epilepsy,
neuropathic pain, and bipolar disorder [1]. In a preclinical collaboration with Eli Lilly, we
developed a promising radioligand, 18F-TARP252 to image TARP >=-8 using positron emission
tomography (PET).
This protocol covers three phases:
- Phase 1: kinetic brain imaging to quantify TARP >=-8 in brain relative to concurrent
measurement of the parent radioligand in arterial plasma;
- Phase 2: if 18F-TARP252 is successful in Phase 1, we will estimate the
radiation-absorbed doses by performing whole body imaging;
- Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the
parent radioligand in arterial plasma.
Study Population
Healthy adult female and male volunteers (n=22, ages 18 - 55) will undergo brain imaging. An
additional eight healthy volunteers will undergo whole body dosimetry analysis.
Design
For quantification of TARP >=-8, 22 healthy controls will have brain PET imaging using
18F-TARP252 and an arterial line. Some of them will have a test-retest scan. Eight additional
subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will
be used.
Outcome Measures
To assess quantitation of TARP >=-8 with 18F-TARP252, we will primarily use two outcome
measures: the identifiability and time stability of distribution volume calculated with
compartmental modeling. In test-retest study, we will calculate the retest variability. We
will assess whole-body biodistribution and dosimetry of 18F-TARP252 by calculating doses to
organs and effective dose to the body.
- INCLUSION CRITERIA:
- Age 18 - 55 (including 18 and 55).
- Able to give written informed consent.
- Healthy
- Enrolled in 01-M-0254
EXCLUSION CRITERIA:
- Any current Axis I diagnosis.
- Clinically significant laboratory abnormalities.
- Positive HIV test.
- Unable to have an MRI scan.
- History of neurologic illness or injury with the potential to affect study data
interpretation.
- Recent exposure to radiation related to research (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.
- Pregnancy or breast feeding.
- Able to get pregnant but does not use birth control.
- Drug/alcohol abuse or dependence
Exclusion criteria for the dosimetry subjects are the same as reported above, with the
exception of MRI contraindications, because an MRI will not be performed in these subjects.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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