Expanding range and functionality of radiotracers for improved disease diagnosis

Biomedical imaging has revolutionized medicine, granting doctors a window into miniscule molecular and cellular processes inside the body. An EU-funded project helped to expand the view, developing innovative radiochemistry concepts and techniques that could lead to earlier diagnosis of diseases - saving lives.

Radiotracers are molecules labeled with radioactive atoms that are essential to precision imaging technologies such as positron emission tomography (PET). By tracking the activity of special radiotracers designed to accumulate in tumors, areas of inflammation or certain types of cells, non-invasive PET imaging scans can detect disease long before it is evident in other tests, including many types of cancer, heart disease and gastrointestinal, endocrine or neurological disorders.

Different radiotracer molecules enable PET machines to track different cells and hence detect various processes occurring in the body with varying levels of clarity. The EU-funded RADIOMI project expanded the range and functionality of radiotracers, improving the imaging available and the ability of pharmacologists to develop and evaluate new treatments.

Among the project’s main achievements was the development of innovative radiochemistry techniques to improve diagnosis, and the monitoring of disease progression or drug discovery using radioactive isotopes of molecules such as fluorine-18, carbon-11 and nitrogen-13.

‘The main limitation in the use of PET is that it requires molecules labeled with short-lived radioactive atoms,’ says RADIOMI coordinator Véronique Gouverneur at the University of Oxford in the UK. ‘The preparation of these labeled molecules is very challenging and involves synthetic strategies and technological resources that differ significantly from classical chemistry. We are therefore addressing one of the key aspects of functional biomedical imaging – the radiochemistry essential for the preparation of radiotracers, many of which are currently difficult to create.’

Innovative techniques

RADIOMI researchers developed simple, fast and efficient techniques to label amino acids with nitrogen-13, turning these ubiquitous essential building blocks of proteins into excellent tracers for investigating metabolic processes via PET scans.

They also developed new fluorine-18 reagents to access radiotracers that are difficult or not possible to obtain via conventional radiochemistry, as well as designing a more efficient process to use carbon-11, a radioisotope essential for diagnosing and monitoring Alzheimer’s disease, among other applications.

The work has opened new pathways for ongoing research by members of the RADIOMI team, including collaboration with a pharmaceutical company to create novel molecules of pharmaceutical interest using carbon-11. Furthermore, two follow-up projects in Spain focused on using nitrogen-13-labeled amino acids to study prostate cancer tumor development.

Another RADIOMI researcher expanded on fundamental work into controlling fluoride reactivity through hydrogen bonding, a discovery that led to the invention of a new class of catalyst with applications in drug discovery.

RADIOMI was funded through the EU’s Marie Skłodowska-Curie fellowship programme and supported young and early-stage researchers in cutting-edge work on radiotracers. The ongoing research by RADIOMI participants underscores the success of the training activities carried out in the project that expanded the career horizons of 18 research fellows across Europe, Gouverneur says.

‘Molecular imaging is a booming research field of critical importance to facilitate diagnosis of disease, to monitor response to therapy, and to streamline the process of drug development with significant social and economic benefits,’ she adds. ‘However, access to trained individuals has been limited and there is intense competition for the same pool of talent in Europe and internationally. RADIOMI has successfully demonstrated how training networks can have a direct positive impact by producing a new crop of highly trained people in radiochemistry, many of whom have gone on to fill important unmet needs in the field.’.

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