EPSRC logo

Details of Grant 

EPSRC Reference: EP/Y001931/1
Title: 18F-Fluorodeamination through Pyridinium Salts: Innovation, Mechanism, and User Guidelines
Principal Investigator: Gouverneur, Professor V
Other Investigators:
Tredwell, Dr M
Researcher Co-Investigators:
Project Partners:
Colorado State University Janssen Research & Development LLC
Department: Oxford Chemistry
Organisation: University of Oxford
Scheme: Standard Research
Starts: 01 April 2024 Ends: 31 March 2027 Value (£): 591,197
EPSRC Research Topic Classifications:
Chemical Synthetic Methodology
EPSRC Industrial Sector Classifications:
Chemicals Pharmaceuticals and Biotechnology
Related Grants:
Panel History:
Panel DatePanel NameOutcome
05 Jul 2023 EPSRC Physical Sciences Prioritisation Panel- July 2023 Announced
Summary on Grant Application Form
"The importance of the physical sciences to advance life sciences has never been greater", and inventive chemistry is continuously needed to program, understand and control function. This proposal fits within this context with innovation in the field of radiochemistry to advance molecular imaging. Positron-emission tomography (PET) is a functional and quantitative molecular imaging technology to interrogate biological processes in vivo, facilitate drug discovery and experimental medicine, enable early-stage clinical trials, and guide clinical practice (e.g. cancer and neurological disorders diagnosis, staging, and response to treatment). Combined with other diagnostic tests, this technology can facilitate for example the diagnosis of cancer, evaluate epilepsy, Alzheimer's disease and coronary artery disease.

PET scans are routinely performed in the clinic and to support pharmaceutical drug discovery programs. A radiopharmaceutical (radioactive tracer) is required to perform these scans because the technique relies on the emission of gamma rays. These radioactive molecules must be prepared in specialist laboratories that performs radiochemistry with a cyclotron-produced positron emitting radioisotope such as commonly used 18F. Since the half-life of 18F is short (just under 110 minutes), the chemistry involved is challenging. Many groups including our laboratory have focused on novel radiochemical transformations for 18F-labelling because fluorine substitution is frequently encountered in pharmaceutical drugs. Labelling strategies that make use of ubiquitous precursors are the most sought-after, especially if these precursors are amenable to divergent radiochemistries. This is exactly what we will achieve with this project.

We propose to develop novel 18F-radiochemistries using ubiquitous primary amines to accelerate PET ligand and radiopharmaceutical discovery. Our strategy consists of converting amines into pyridinium salts that are highly versatile synthetic intermediates acting either as electrophiles or as redox-active precursors. This rich reactivity profile offers the possibility to access a large diversity of 18F-labelled molecules through either direct 18F-fluorination or 18F-fluoroalkylation/arylation from primary amines. Such radiochemistry will streamline access to molecules that are either difficult to label or not possible to label with current technologies. All labelling reactions will be performed on an automated platform that is widely used in the UK and in the world. This aspect of the project is very important to ensure rapid translation of the novel radiochemistry proposed from a research laboratory to the clinic for immediate impact and use to improve patient healthcare, and ultimately for the manufacturing of new PET diagnostics or radioligands.
Key Findings
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Potential use in non-academic contexts
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Description This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Date Materialised
Sectors submitted by the Researcher
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Project URL:  
Further Information:  
Organisation Website: http://www.ox.ac.uk