The synthesis and validation of multimodal PET/fluorescence zinc sensing probes as potential imaging agents for prostate cancer

Firth, George

Abstract

Prostate cancer (PCa) is the 2nd most common cancer worldwide for males, and the 4th most common cancer overall, accounting for 15% of all male cancers in 2012. PCa is asymptomatic in its early stages, advances in medical imaging are improving diagnosis, however novel simple medical imaging agents are needed to diagnose the disease early. A fluorescent imaging probe, 2-((2-(2-fluoroethoxy)ethyl)amino)-N-(quinolin-8-yl)acetamide (AQA-F), that changes emission profile when binding the metal zinc has been synthesised. A Stokes shift of 80 nm can be observed upon zinc binding, enhancing the emission wavelength from 420 to 500 nm, with a Kd of 14x10⁻⁶ M. It was shown that AQA-F has the highest affinity for Zn²⁺ which will allow for the in vitro differentiation of zinc bound and free probe. AQA-F was non-toxic at imaging concentrations in healthy prostate, prostate cancer and healthy tissues. It was also shown that AQA-F was internalised by healthy and prostate cancer cell lines across both 2D and 3D models. This allows for the probe to function as an endogenous zinc sensor in vitro with the potential of being translated into clinical use for the diagnosis of prostate cancer in men. Further studies will be required to identify a radiolabelling procedure for the probe with ¹⁸F to enable possible dual modal imaging.

Citation

Firth, G. The synthesis and validation of multimodal PET/fluorescence zinc sensing probes as potential imaging agents for prostate cancer. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4221824

• Thesis Type: Thesis
• Deposit Date: Oct 2, 2019
• Publicly Available Date: Feb 23, 2023
• Keywords: Biological sciences
• Public URL: https://hull-repository.worktribe.com/output/4221824
• Additional Information: School of Life Sciences, The University of Hull
• Award Date: Aug 1, 2017