PET Whole Body Imaging Using a Peripheral Benzodiazepine Receptor Ligand [C-11]PBR28

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by National Institutes of Health Clinical Center (CC)
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: December 2, 2006
Last updated: September 24, 2015
Last verified: September 2015
In this study we will examine where the radioactive tracer [11C]PBR28 is distributed in the body of healthy volunteers to calculate the radiation exposure to organs of the body. We will also test if [11C]PBR28 binds to your blood cells and compare with the binding in PET images.

Condition Intervention Phase
Drug: [C-11]PRB28
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: PET Whole Body Imaging Using a Peripheral Benzodiazepine Receptor Ligand [C-11]PBR28

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Biodistribution of [C-11]PBR28

Estimated Enrollment: 100
Study Start Date: November 2006
Estimated Study Completion Date: September 2017
Detailed Description:

The peripheral benzodiazepine receptor (PBR) is distinct from central benzodiazepine receptors associated with GABA(A) receptors. Although PBR was initially identified in peripheral organs such as kidneys, endocrine glands and lungs, later studies identified PBR in the central nervous system. In normal conditions, PBR is expressed in low levels in some neurons and glial cells. PBR can be a clinically useful marker to detect neuroinflammation because activated microglial cells in inflammatory areas express much greater levels of PBR than in microglial cells in resting conditions.

PBR has been imaged with positron emission tomography (PET) using [(11)C]1-(2-chlorophenyl-N-methylpropyl)-3-isoquinoline carboxamide (PK11195). However, this classical ligand provides only low levels of specific signals and is not sensitive to detect changes that occurred in vivo. Recently we developed a new ligand, N-acetyl-N-(2-[(11)C]methoxybenzyl)-2-phenoxy-5-pyridinamine [(11)C]PBR28), which showed much greater specific signals than [(11)C]PK11195 in non-human primates. Therefore, [(11)C]PBR28 is a promising PET ligand. However, radiation absorbed doses have not been estimated from human whole body imaging.

The initial purpose of this protocol is to estimate radiation absorbed doses of [11C]PBR28 by performing whole body imaging studies on ten healthy human subjects. The radiation absorbed doses are required to apply this PET ligand in various neurological and psychiatric disorders in the future.

Under the current and other protocols using [(11)C]PBR28, we found that some healthy subjects and patients have very low to no binding of [(11)C]PBR28. We studied approximately 188 subjects in total under protocols using [11C]PBR28 and found that 8.5% (16/188) had almost no binding of [(11)C]PBR28. Several published ligands have been tested and all of the tested ligands recently developed show low affinity to a subset of humans. By using [(11)C]PBR28, we need to exclude PBR28 nonbinders from the data to study changes in PBR. By using a PET ligand that binds equally to PBR28 binders and nonbinders, we would be able to study all subjects. We also confirmed that PBR28 nonbinders determined by PET do not show binding in in vitro binding assays using blood cells.

We wish to test new ligands currently being developed in our chemistry group by obtaining blood samples from additional PBR28 nonbinders (= low affinity binders) and by performing in vitro binding assays. Because our preliminary analysis of whole body imaging has shown that the differences between PBR28 binders and nonbinders might somewhat vary among organs and the cause of the nonbinding phenomenon is not fully understood, after identifying PBR28 nonbinders by binding assays, we will perform whole body imaging using [(11)C]PBR28.


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes

All subjects must be healthy and aged 18-65 years.


  • Current psychiatric disease, substance abuse or severe systemic disease based on history and physical exam.
  • Laboratory tests with clinically significant abnormalities.
  • Prior participation in other research protocols or clinical care in the last year such that radiation exposure including that from this protocol would exceed the guidelines set by the Radiation Safety Committee (RSC).
  • Pregnancy and breast feeding.
  • Positive HIV test.
  • Cannot lie flat for 2 - 3 h.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00407693

Contact: Maria D Ferraris Araneta, C.R.N.P. (301) 496-9423
Contact: Masahiro Fujita, M.D. (301) 451-8898

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Principal Investigator: Masahiro Fujita, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications: Identifier: NCT00407693     History of Changes
Other Study ID Numbers: 070035  07-M-0035 
Study First Received: December 2, 2006
Last Updated: September 24, 2015
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Effective Dose
Radiation-Absorbed Dose processed this record on February 08, 2016