NCT02108015

Evaluation of a Novel Positron Emission Tomography (PET Radiotracer for TARP Gamma-8

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: National Institute of Mental Health (NIMH) · NIH
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
PROCEDURE	Brain Imaging (PET)
PROCEDURE	Aterial Line
PROCEDURE	Blood Sampling

Timeline

• Start date: 2014-03-05
• Primary completion: 2014-09-05
• Completion: 2016-12-01
• First posted: 2014-04-09
• Last updated: 2019-11-20

Locations

1 site across 1 country: United States