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.

Abstract

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.

• Authors: Dewei Tang, Michael L Nickels, M Noor Tantawy, Jason R Buck, H Charles Manning
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 16 Issue 6 Pg. 813-20 (Dec 2014) ISSN: 1860-2002 [Electronic] United States
• PMID: 24845529 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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