Preclinical imaging evaluation of novel TSPO-PET ligand 2-(5,7-Diethyl-2-(4-(2-[(18)F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([ (18)F]VUIIS1008) in glioma

Mol Imaging Biol. 2014 Dec;16(6):813-20. doi: 10.1007/s11307-014-0743-2.


Purpose: Translocator protein (TSPO) concentrations are elevated in glioma, suggesting a role for TSPO positron emission tomography (PET) imaging in this setting. In preclinical PET studies, we evaluated a novel, high-affinity TSPO PET ligand, [(18)F]VUIIS1008, in healthy mice and glioma-bearing rats.

Procedures: Dynamic PET data were acquired simultaneously with [(18)F]VUIIS1008 injection, with binding reversibility and specificity evaluated in vivo by non-radioactive ligand displacement or blocking. Compartmental analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry.

Results: [(18)F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [(18)F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [(18)F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [(18)F]DPA-714.

Conclusions: The PET ligand [(18)F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Carrier Proteins / metabolism*
  • Fluorine Radioisotopes* / pharmacokinetics
  • Glioma / diagnostic imaging
  • Glioma / metabolism*
  • Glioma / pathology
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Positron-Emission Tomography / methods*
  • Pyrazoles* / pharmacokinetics
  • Pyrimidines* / pharmacokinetics
  • Rats
  • Rats, Wistar
  • Receptors, GABA / metabolism*
  • Receptors, GABA-A / metabolism*


  • Bzrp protein, mouse
  • Carrier Proteins
  • Fluorine Radioisotopes
  • Ligands
  • N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide
  • Pyrazoles
  • Pyrimidines
  • Receptors, GABA
  • Receptors, GABA-A
  • Tspo protein, rat