Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation

J Cereb Blood Flow Metab. 2010 Sep;30(9):1608-18. doi: 10.1038/jcbfm.2010.63. Epub 2010 Apr 28.


[(11)C]PBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for [(11)C]PK11195, another TSPO radioligand. We measured the specific binding signals with [(3)H]PK11195 and [(3)H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [(3)H]PBR28, although all samples showed [(3)H]PK11195 binding. There was a marked reduction in the affinity of [(3)H]PBR28 for TSPO in samples with no visible [(3)H]PBR28 autoradiographic signal (K(i)=188+/-15.6 nmol/L), relative to those showing normal signal (K(i)=3.4+/-0.5 nmol/L, P<0.001). Of this latter group, [(3)H]PBR28 bound with a two-site fit in 40% of cases, with affinities (K(i)) of 4.0+/-2.4 nmol/L (high-affinity site) and 313+/-77 nmol/L (low-affinity site). There was no difference in K(d) or B(max) for [(3)H]PK11195 in samples showing no [(3)H]PBR28 autoradiographic signal relative to those showing normal [(3)H]PBR28 autoradiographic signal. [(3)H]PK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in [(11)C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoradiography
  • Binding Sites
  • Binding, Competitive / drug effects
  • Brain / diagnostic imaging*
  • Brain Chemistry
  • Carbon Radioisotopes
  • Female
  • Humans
  • Immunohistochemistry
  • Isoquinolines
  • Male
  • Membranes / diagnostic imaging
  • Membranes / metabolism
  • Middle Aged
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism
  • Neuritis / diagnostic imaging*
  • Positron-Emission Tomography*
  • Pyridines / metabolism*
  • Radioligand Assay
  • Receptors, GABA / metabolism*
  • Tissue Banks


  • Acetamides
  • Carbon Radioisotopes
  • Isoquinolines
  • N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide
  • Nerve Tissue Proteins
  • Pyridines
  • Receptors, GABA
  • TSPO protein, human
  • PK 11195