Synthesis and evaluation of pyrazolopyrimidinyl-based TSPO ligands for cancer imaging

Abstract

This project is focused on PET probe development for cancer imaging by targeting a potential cancer biomarker- Translocator Protein (TSPO). In this project, I evaluated 18F-DPA-714, a pyrazolopyrimindine probe, as a TSPO PET probe for C6 glioma preclinical imaging. With in vivo PET imaging study, I evaluated 18F-DPA-714 as a promising tracer in detecting C6 glioma in rats. With following optimization of this probe, I discovered 18F-VUIIS1008, a TSPO PET probe featuring a 36-fold higher binding affinity compared to 18F-DPA-714. Further preclinical PET imaging with 18F-VUIIS1008 demonstrated a partial reversible binding profile to tumor instead of the healthy brain. Meanwhile, I also found that 18F-VUIIS1008 demonstrated a higher in vivo stability and lower brain uptake compared to 18F-DPA-714. According to these result, we envision this 18F-VUIIS1008 holds a great potential to serve as a PET probe for the human glioma imaging.