Yunkou Wu, M.D., Ph.D.
Yunkou Wu is focusing his research on the design and synthesis of new agents for molecular imaging of cancer. Modern clinical cancer treatments rely heavily on the precise detection of malignancies with medical molecular imaging agents and technologies. Even though the remarkable advances have been made in molecular imaging during the past decades, the accurate evaluations of the tumors to pinpoint the tumor type and morphology at an early stage are still very challenging.
Studies have shown that the extracellular pH (pHe) of solid tumors is acidic as result of cellular adaptations for fast glycolysis. This means tissue pH measurement can be used as a way to diagnose tumors. Thus, it is very import to develop molecular imaging agents that can accurately measure pH over pH range of 6.0-7.2.
Currently, quantitative CEST pH sensing has only been achieved by using a cocktail of agents having weakly shifted –NH protons for ratiometric imaging, wherein one proton exchange pool is used as the CEST pH sensor and another pool as a concentration marker. Dr. Wu is developing single agent based systems for molecular imaging of pHe. For instance, under the supervision of Dean Sherry, Ph.D., he has developed novel PARACEST agents that are responsive to pH. The new agent has an exchanging Eu3+-bound water resonance that shifts (50-55 ppm) with a change in pH. This feature allows a direct measure of pH in a single experiment by ratiometric imaging.
The applications of CEST agents for molecular imaging are limited by the low sensitivity of CEST technique. Dr. Wu is synthesizing polymeric PARACEST agents that contain a large numbers of exchangeable groups to improve CEST contrast sensitivity. Results show that the polymeric agents have a much lower detection limit in the range of 60~130 uM compared 1300~1700 uM for the monomer. He is also working on the introduction of tumor targeted ligands such as folic acid or RGD to the polymeric PARACEST agents. The resulting polymeric conjugations are expected to be able to image tumors with CEST or PET.
Hypoxia occurs when a tumor outgrows its vascular supply, so the tumor hypoxia detection with molecular imaging agent has significant implications for cancer diagnosis and treatment. Dr. Wu is in collaboration with Xiankai Sun, Ph.D., to develop tumor hypoxia targeted agents. The detection flexibilities are greatly improved by incorporating multiple imaging modalities including MRI, PET and optical imaging into a single agent.
For publication information please view Dr. Wu's faculty profile.