Kinetic evaluation in nonhuman primates of two new PET ligands for peripheral benzodiazepine receptors in brain

Synapse. 2007 Aug;61(8):595-605. doi: 10.1002/syn.20394.

Abstract

Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia and are, thereby, biomarkers of cellular inflammation in brain. We recently developed two PET ligands with an aryloxyanilide structure to image PBRs and now evaluate the kinetics of these radiotracers in monkey to determine whether they are suitable to explore in human. Baseline and receptor-blocking scans were performed with [(11)C]PBR01 and [(18)F]PBR06 in conjunction with serial measurements of the arterial plasma concentration of parent radiotracer separated from radiometabolite. We used brain and plasma data with compartmental modeling to calculate regional brain distribution volume, which is equal to the ratio at equilibrium of the concentration of radioligand in brain to that of plasma. The distribution volume of [(11)C]PBR01 was inaccurately estimated in the baseline scans, possibly because of the short half-life of (11)C or the presence of radiometabolite in brain. In contrast, the distribution volume of [(18)F]PBR06 was stably determined within 200 min of scanning, and nondisplaceable uptake was only approximately 10% of total brain uptake. [(18)F]PBR06 is promising for use in human because brain activity could be quantified with standard compartmental models and showed higher ratios ( approximately 10:1) of specific to nonspecific uptake. A critical factor for human use will be whether the tracer has adequately fast wash out from brain relative to the half-life of the radionuclide to obtain stable values of distribution volume.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Anilides / blood
  • Anilides / pharmacokinetics*
  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Fluorine Radioisotopes / blood
  • Fluorine Radioisotopes / pharmacokinetics
  • Ligands
  • Macaca mulatta
  • Positron-Emission Tomography*
  • Radiopharmaceuticals / blood
  • Radiopharmaceuticals / pharmacokinetics*
  • Receptors, GABA-A / metabolism*
  • Tissue Distribution

Substances

  • Anilides
  • Fluorine Radioisotopes
  • Ligands
  • Radiopharmaceuticals
  • Receptors, GABA-A