Preclinical Evaluation of a Novel TSPO PET Ligand 2-(7-Butyl-2-(4-(2-[18F]Fluoroethoxy)phenyl)-5-Methylpyrazolo[1,5-a]Pyrimidin-3-yl)-N,N-Diethylacetamide (18F-VUIIS1018A) to Image Glioma

These studies illustrate that [18F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors.

In this study, we synthesized [19F]VUIIS1018A and the precursor for radiosynthesis of [18F]VUIIS1018A. TSPO binding affinity was confirmed using a radioligand competitive binding assay in C6 glioma cell lysate. Further, dynamic imaging studies were performed in rats using a microPET system. These studies include displacement and blocking studies for ligand reversibility and specificity evaluation, and compartment modeling of PET data for pharmacokinetic parameter measurement using metabolite-corrected arterial input functions and PMOD.

There is an urgent need for the development of novel positron emission tomography (PET) tracers for glioma imaging. In this study, we developed a novel PET probe ([18F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical study was to evaluate this novel TSPO probe for glioma imaging. Procedures: In this study, we synthesized [19F]VUIIS1018A and the precursor for radiosynthesis of [18F]VUIIS1018A. TSPO binding affinity was confirmed using a radioligand competitive binding assay in C6 glioma cell lysate. Further, dynamic imaging studies were performed in rats using a microPET system. These studies include displacement and blocking studies for ligand reversibility and specificity evaluation, and compartment modeling of PET data for pharmacokinetic parameter measurement using metabolite-corrected arterial input functions and PMOD.

Compared to previously reported TSPO tracers including [18F]VUIIS1008 and [18F]DPA-714, the novel tracer [18F]VUIIS1018A demonstrated higher binding affinity and BPND. Pretreatment with the cold analog [19F]VUIIS1018A could partially block tumor accumulation of this novel tracer. Further, compartment modeling of this novel tracer also exhibited a greater tumor-to-background ratio, a higher tumor binding potential and a lower brain binding potential when compared with other TSPO probes, such as [18F]DPA-714 and [18F]VUIIS1008. Conclusions: These studies illustrate that [18F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors.