PET Imaging of Peripheral Benzodiazepine Receptors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00696371
First received: June 11, 2008
Last updated: August 20, 2014
Last verified: August 2014

June 11, 2008
August 20, 2014
June 2008
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The first goal of this study is to compare [11C]PBR28 and [11C](R)-PK 11195 as radioligands in the measurement of PBR in healthy human subjects. Our primary outcome measures will be the distribution volume and time stability of each radioligand.
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Complete list of historical versions of study NCT00696371 on ClinicalTrials.gov Archive Site
The second goal is to identify non-binders, that is, subjects that do not demonstrate any binding to [11C]PBR28.
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PET Imaging of Peripheral Benzodiazepine Receptors
PET Imaging of Peripheral Benzodiazepine Receptors Using [11C](R)-PK 11195 and [11C]PBR28

This study will use positron emission tomography (PET) to measure a receptor in the brain that is involved in inflammation. It will test two radioactive chemicals used in the procedure to see if the newer chemical, [(11)C]B, is as good or better than the older one, [(11)C]A, for measuring brain inflammation.

Healthy volunteers 18 years of age and older may be eligible for this study. Participants undergo an evaluation, [(11)C]A PET scan, [(11)C]B PET scan and magnetic resonance imaging (MRI), as follows:

Evaluation

Medical history and physical examination, blood and urine tests

PET scans

  • [(11)C]A scan. A catheter (plastic tube) is placed in an arm vein for injection of the [(11)C]A isotope. Some patients also have a catheter placed in an artery in the wrist to collect arterial blood samples during the scan. Subjects then lie on the scanner bed and a special mask is fitted to the head to help keep the subject s head still during the procedure. Following an 8-minute scan to calibrate the scanner, the [(11)C]A is injected into the catheter in the vein and pictures are taken that show where chemicals related to inflammation are present. The procedure takes about 2.5 hours.
  • [(11)C]B scan. The procedure is the same as above for [(11)C]A, except the isotope used is [(11)C]B.

MRI scan.

This test uses a strong magnetic field and radio waves to obtain images of body organs and tissues. The subject lies on a table that can slide in and out of the scanner (a metal cylinder), wearing earplugs to muffle loud noises that occur during the scan.

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Objective:

In response to brain inflammation, microglia over-express the peripheral benzodiazepine receptor (PBR). Although peripheral organs such as the heart and kidney express PBR constitutively, the brain normally expresses PBR in low numbers. Increased PBR density in the brain therefore signifies a change from a normal state to an active, inflammatory state. Positron emission tomography (PET) imaging can quantify PBR density in vivo using radioligands that bind to PBR sites. One PBR-selective radioligand, [(11)C](R)-PK 11195, has been used to identify areas of brain inflammation in patients with various neurological diseases. Unfortunately, [(11)C](R)-PK 11195 has several limitations, including low specific signal. A recently developed radioligand, [(11)C]PBR28, has higher specificity than [(11)C](R)-PK 11195 for PBR in animal studies. No study to date has compared [(11)C]PBR28 to [(11)C](R)-PK 11195 in human subjects.

In early clinical studies using [(11)C]PBR28, 4 of 32 healthy human subjects had complete absence of radioligand binding, even in peripheral organs that constitutively express PBR. One of these non-binders had specific binding of PBR28 on an in vitro assay using peripheral lymphocytes. We do not know why some subjects have [(11)C]PBR28 binding while others do not. We also do not know why one non-binder had positive in vitro binding and negative in vivo binding on PET imaging. No study has reported absent binding with [(11)C](R)-PK 11195. In order to better understand the phenomenon of non-binding, we need to obtain [(11)C](R)-PK 11195 PET scans in subjects that are [(11)C]PBR28 non-binders.

Study Population:

This protocol will study a total of 30 healthy human volunteers.

Design:

Fifteen subjects will undergo PET imaging with [(11)C]PBR28 and [(11)C](R)-PK 11195 using arterial blood sampling for fully quantitative image analysis. These subjects may have dedicated brain PET imaging or whole body PET imaging.

Fifteen subjects will undergo PET imaging with [(11)C]PBR28 and [(11)C](R)-PK 11195 without arterial blood sampling. These subjects will have whole body PET imaging.

All subjects will have in vitro PBR28 binding assays performed.

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Outcome Measures:

Our primary outcome measures will be the distribution volume and time stability of each radioligand. We also wish to determine if subjects with absent [(11)C]PBR28 binding also have absent [(11)C](R)-PK 11195 binding. The presence or absence of [(11)C]PBR28 and [(11)C](R)-PK 11195 binding will be evaluated in brain and in peripheral organs. Lastly, we will measure in vitro binding of PBR28 by performing binding assays using peripheral blood cells.

Observational
Time Perspective: Prospective
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Healthy
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
August 2014
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  • INCLUSION CRITERIA:
  • Subjects must be healthy and at least 18 years of age.

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 or breast feeding.
  • Positive result on urine screen for illicit drugs.
  • Subjects who cannot lie on their back for extended periods of time.
  • Subjects with significant claustrophobia who cannot tolerate an MRI scan.
  • Subjects with cardiac pacemakers or metal in their bodies.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00696371
080158, 08-M-0158
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National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
National Institute of Mental Health (NIMH)
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Principal Investigator: William C Kreisl, M.D. National Institute of Mental Health (NIMH)
National Institutes of Health Clinical Center (CC)
August 2014

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