Specific PET Radioligand Binding to Translocator Protein
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|ClinicalTrials.gov Identifier: NCT02181582|
Recruitment Status : Completed
First Posted : July 4, 2014
Last Update Posted : September 27, 2018
- A brain protein called translocator protein (TSPO) shows changes in some brain diseases. A radioactive drug called 11C-(R)-PK 11195 is used to take pictures of TSPO using a camera called positron emission tomography (PET). Researchers want to find out how well 11C-(R)-PK 11195 takes the pictures.
- To evaluate the radioactive chemical 11C-(R)-PK 11195.
- Healthy volunteers ages 18-55.
- Participants will be screened with a medical exam.
Participants will have scans at up to 4 visits.
PET scan using 11C-(R)-PK 11195:
- A small tube (catheter) will be put into an artery at the wrist or elbow, by a needle. The needle will be removed, leaving only the catheter in the artery. Blood samples will be taken through this catheter.
- Another catheter will be placed into a vein in the arm or hand.
- 11C-(R)-PK 11195 will be injected through the second catheter.
- The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of it. They may get a plastic mask for their face and head.
- Participants will receive a dose of emapunil by mouth. Participants will then have another PET scan.
- Participants may have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder surrounded by a magnetic field. The participant will lie on a table that can slide in and out of the cylinder. Participants will get earplugs for the loud knocking noises.
- After each scan, participants will get a follow-up phone call. Two to seven days after taking emapunil, participants will return for a follow-up visit.
|Condition or disease||Intervention/treatment||Phase|
|Baseline Blocking Receptor Binding||Drug: Emapunil Device: PET||Phase 1|
The 18kDa Translocator Protein (TSPO, formerly known as the peripheral benzodiazepine receptor (PBR)) is expressed in activated microglia and reactive astrocyte. It has therefore been used as an imaging target for positron emission tomography (PET) to investigate diseases involving microglial activation and/or macrophage recruitment, such as multiple sclerosis, herpes encephalitis, Parkinson s disease, Alzheimer s disease and ischemic stroke. The vast majority of PET studies reported to date have used 11C-(R,S) and 11C-(R)-PK 11195, a 3-isoquinolinecarboxamide antagonist, with nanomolar affinity for TSPO. Several second generation radioligands, including 11C-PBR28, 11C-DPA-713, and 11C-ER176 have been developed. Although these ligands have greater signal to noise (specific to nondisplaceable uptake) ratio than 11C-(R)-PK 11195,their binding to TSPO is affected by a single nucleotide polymorphism (SNP). Specific to nondisplaceable ratio of 11C-PBR28 has recently been reported. However, no one has ever measured the specific to nondisplaceable ratio of other TSPO radioligands including 11C-(R)-PK 11195, 11C-DPA-713 and 11C-ER176 in human subjects. In addition, differences in this binding site between species preclude comparisons based on studies in animals. The purposes of this study are to measure the signal to noise ratio (i.e., ratio of specific to non-displaceable uptake) of 11C-(R)-PK 11195, 11C-ER176 and 11C-DPA-713 in human subjects with two scans in each subject: at baseline and after emapunil, an agonist at the TSPO site and a putative anxiolytic based on studies in animals and in humans and study the effect of the SNP on the in vivo specific binding of the PET ligands.
75 healthy volunteers in total aged 18 to 55 years. Of these, 25 will have 11C-(R)-PK 11195, 25 have 11C-DPA-713 scans, and 25 have 11C-ER176.
Healthy volunteers (n = up to 25) will have two scanning sessions using 11C-(R)-PK 11195: a) baseline i.e., medication-free and b) blocking i.e. with medication. For blocking, we will give one oral dose of emapunil (15 or 90 mg), about 1.5 hours before the second injection of the radioligand. Both scanning sessions would include an arterial line and measurement of the input function of parent radioligand separated from radiometabolites as well as plasma free fraction of radioligand. Additional 25 healthy volunteers will have two scanning sessions using 11C-DPA-713 in the same design, one baseline and another after one oral dose of emapunil. An additional 25 healthy volunteers will have two scanning sessions using 11C-ER176 in the same design, one baseline and another after one oral dose of emapunil. The total number of participants is 75 (= 25 + 25 + 25)
Baseline scans measure total binding i.e., total distribution volume (V[T]). By applying the Lassen plot, combined data from both baseline scans and those with administration of emapunil measure nonspecific binding i.e., nondisplaceable distribution volume (V[ND]). From these V[T] and V[ND] values, specific-to-nondisplaceable ratios will be calculated as (V[T] V[ND]) / V[ND[ and the influence of the SNP to specific binding, V[S] = V[T] - VND will also be studied.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of Specific PET Radioligand Binding To Translocator Protein|
|Study Start Date :||June 24, 2014|
|Actual Primary Completion Date :||June 16, 2016|
|Actual Study Completion Date :||November 23, 2016|
Experimental: Emapunil Administration
Single Arm Study
Single peroral administration
Positron emission tomography, which creates images by detecting radioactivity.
- Signal noise ratio [C-11](R)-PK 11195 [ Time Frame: 2 moths ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02181582
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Masahiro Fujita, M.D.||National Institute of Mental Health (NIMH)|