Determination of [(11)C]PBR28 binding potential in vivo: a first human TSPO blocking study

J Cereb Blood Flow Metab. 2014 Jun;34(6):989-94. doi: 10.1038/jcbfm.2014.46. Epub 2014 Mar 19.


Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [(11)C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [(11)C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [(11)C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands.

Publication types

  • Clinical Trial

MeSH terms

  • Acetamides / administration & dosage*
  • Adult
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Carbon Isotopes / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Female
  • Humans
  • Male
  • Positron-Emission Tomography*
  • Purines / administration & dosage
  • Pyridines / administration & dosage*
  • Radiography
  • Receptors, GABA / metabolism*


  • Acetamides
  • Carbon Isotopes
  • N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide
  • N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide
  • Purines
  • Pyridines
  • Receptors, GABA
  • TSPO protein, human