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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
Authors:Dewei Tang  Michael L Nickels  M Noor Tantawy  Jason R Buck  H Charles Manning
Institution:1. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232-2310, USA
2. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
3. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
4. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
5. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232, USA
6. Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
7. Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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.
Keywords:
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