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

    Tang, Dewei
    : https://etd.library.vanderbilt.edu/etd-03252013-153516
    http://hdl.handle.net/1803/11305
    : 2013-04-15

    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.
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