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Title page for ETD etd-03252013-153516


Type of Document Dissertation
Author Tang, Dewei
Author's Email Address acetdw@gmail.com
URN etd-03252013-153516
Title Synthesis and evaluation of pyrazolopyrimidinyl-based TSPO ligands for cancer imaging
Degree PhD
Department Chemical and Physical Biology
Advisory Committee
Advisor Name Title
H.Charles Manning Committee Chair
Brian O. Bachmann Committee Member
John C. Gore Committee Member
Robert J. Coffey Committee Member
Thomas E. Yankeelov Committee Member
Keywords
  • TSPO
  • Cancer Imaging
  • Pyrazolopyrimidines
  • Positron Emission Tomography
  • DPA-714
  • Glioma
Date of Defense 2013-03-18
Availability unrestricted
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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