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Microfluidic Based Reactions with [18F]Fluoroform: A Toolbox for Next Generation 18F-Radiolabelled Medicinal Chemistry Compounds

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  • Full or part time
    Dr P. Miller
    Dr G Smith
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

This project aims to develop the technology and labelling chemistry to facilitate the trapping and direct reaction of [18F]fluoroform. This will enable us to fully exploit [18F]fluoroform for developing [18F]CF3 PET radiotracers relevant to oncology.

The trifluoromethyl group (-CF3) is a key medicinal chemistry bioisostere used to alter the bioavailability, metabolic stability, affinity and lipophilicity of pharmaceuticals. It is found in a number of top-selling drug molecules, including: fluoxetine, celecoxib and efavirenz. The CF3 group is also now a desirable group to radiolabel with fluorine-18 for the development of Positron Emission Tomography (PET) tracers. Recently, the reaction of [18F]fluoroform ([18F]CHF3) has been realised as viable route for the incorporation of [18F]CF3 groups into potential PET tracers. [18F]Fluoroform, however, is a very challenging reagent to generate, process and react owing to its volatility and chemical inertness. This project will apply microfluidic technology to overcome these challenges in order to trap and react [18F]CHF3 in a safe, efficient and reproducible way for the development of F-18 PET tracers. Microfluidic reactors have key advantages over ‘batch’ labelling methods for handling small volumes of gases and liquids, shielding from radioactivity, and for enhancing mass and heat transfer. We anticipate that reactions can be more rapidly processed and purified compared to batch methods, and that the improved heat and mass transfer rates within the microchannel will further enhance the reaction of [18F]fluoroform, leading to improved yields and molar activities. To demonstrate a proof-of-principle process, we will apply the technology to model substrate compounds before translating to biologically active compounds. A library of selected target molecules includes the key established oncology drugs: endobosarm, buparlisib, sorafenib and regorafenib. This is a multidisciplinary project that will comprise elements of chemistry, radiochemistry, microfluidics/flow chemistry, and PET biology/imaging.

Download a PDF of the complete project proposal: https://d1ijoxngr27nfi.cloudfront.net/docs/default-source/studying-at-the-icr/3_miller_smith_imperial-icr-studentship.pdf?sfvrsn=d1685e69_2

Funding Notes

Full funding is available

Candidate profile

Suitable for a candidate with a background in Life Science, Chemistry, Radiochemistry, Imaging Sciences or PET.

How to apply

Full details about these studentship projects, and the online application form, are available on our website, at: www.icr.ac.uk/phds Applications for all projects should be made online. Please ensure that you read and follow the application instructions very carefully.

Closing date: Monday 3rd December 2018

Please apply via the ICR vacancies web portal
https://apply.icr.ac.uk/

email contact: [Email Address Removed]
supervisor emails [Email Address Removed] and [Email Address Removed]


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