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Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[18F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1008) in Glioma

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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, [18F]VUIIS1008, in healthy mice and glioma-bearing rats.

Procedures

Dynamic PET data were acquired simultaneously with [18F]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

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

Conclusions

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

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Acknowledgments

The authors thank George H. Wilson and Daniel Colvin for the assistance with microPET and MR imaging studies, respectively, Allie Fu for preclinical model support, and Matthew R. Hight and Michael L. Schulte for editing the manuscript and helpful discussions. The authors acknowledge funding from the National Institutes of Health (K25 CA127349, P50 CA128323, S10 RR17858, U24 CA126588, 1R01 CA163806) and the Kleberg Foundation.

Conflict of Interest

The authors do not have any conflicts of interest.

Author information

Authors and Affiliations

  1. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232-2310, USA

    Dewei Tang, Michael L. Nickels, M. Noor Tantawy, Jason R. Buck & H. Charles Manning

  2. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Dewei Tang, Michael L. Nickels, M. Noor Tantawy, Jason R. Buck & H. Charles Manning

  3. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

  4. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

  5. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232, USA

    H. Charles Manning

  6. Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

  7. Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

Authors
  1. Dewei Tang
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Correspondence to H. Charles Manning.

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Tang, D., Nickels, M.L., Tantawy, M.N. et al. Preclinical Imaging Evaluation of Novel TSPO-PET Ligand 2-(5,7-Diethyl-2-(4-(2-[18F]fluoroethoxy)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([18F]VUIIS1008) in Glioma. Mol Imaging Biol 16, 813–820 (2014). https://doi.org/10.1007/s11307-014-0743-2

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