PET Whole Body Imaging Using a Peripheral Benzodiazepine Receptor Ligand [C-11]PBR28
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): [C-11]PRB28
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Dosimetry; Effective Dose; Radiation-Absorbed Dose