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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00407693
First received: December 2, 2006
Last updated: November 22, 2014
Last verified: October 2014

December 2, 2006
November 22, 2014
November 2006
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Biodistribution of [C-11]PBR28
Same as current
Complete list of historical versions of study NCT00407693 on ClinicalTrials.gov Archive Site
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PET Whole Body Imaging Using a Peripheral Benzodiazepine Receptor Ligand [C-11]PBR28
PET Whole Body Imaging Using a Peripheral Benzodiazepine Receptor Ligand [C-11]PBR28

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Healthy
Drug: [C-11]PRB28
N/A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
September 2017
Not Provided
  • INCLUSION CRITERIA:

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

EXCLUSION CRITERIA:

  • 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.
Both
18 Years to 65 Years
Yes
Contact: Maria D Ferraris Araneta, C.R.N.P. (301) 496-9423 ferrarism@mail.nih.gov
Contact: Masahiro Fujita, M.D. (301) 451-8898 fujitam@intra.nimh.nih.gov
United States
 
NCT00407693
070035, 07-M-0035
Not Provided
Not Provided
National Institute of Mental Health (NIMH)
Not Provided
Principal Investigator: Masahiro Fujita, M.D. National Institute of Mental Health (NIMH)
National Institutes of Health Clinical Center (CC)
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP