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EVERYTHING IS ILLUMINATED

The development of cancer is just one of many processes that could be understood better, and the disease fought more effectively, following advances in bioimaging technology.

mvendrel

A new fluorescent tagging technology that will allow medics to detect disease earlier and track the effects of treatment in real time has been pioneered by a team in Scotland.

The hope is that it will eventually be possible to introduce the technology into the human body, so that disease progression can be monitored using existing clinical imaging systems, such as PET scans. Leading the team behind the work is Dr Marc Vendrell, a lecturer in biomedical imaging at the University of Edinburgh.

A chemist by training, it was Dr Vendrell’s work with fl ourophores and imaging in his PhD that sparked an interest in the interface between chemistry and biology.

The vision

A fascination with visualising cells and observing processes within cells using fluorescence took him to the Far East to work at the Singapore Bioimaging Consortium. The philosophy there was to bring together a multidisciplinary team of chemists, physicists, medics and biologists, to develop innovative imaging platforms.

“By then, I was very interested in translating the imaging discoveries as close to clinical applications as is possible, which was why I moved to Edinburgh in 2012 to found the research group there,” he says. “The vision I had was to translate fluorescent chemical probes into clinical imaging, so that we could solve medical problems directly in humans.”

There is a well-established and proven technology that can enhance the resolution and information that can be extracted from basic microscopy studies in cells. The work being carried out by Dr Vendrell and his team in Edinburgh is hoped to translate this knowledge, in conjunction with the use of chemical compounds, into clinical environments.

Seeing peptides

“We want to be able to see how peptides move and function,” he says. “Cells use them to communicate between each other, and this can be very powerful, because it can provide information about both diseased and healthy cells. It can be
very useful for diagnosis and monitoring treatment and helping to understand the fundamental science behind disease.”

The problem has always been that peptides were not easy to see under a microscope, because they are very poorly fluorescent. There has been a lot of work carried out over the last 30 years to make peptides more visible by attaching
chemicals and fluorophores to them to make them highly visible.

The trouble with these conventional strategies has been that the attaching chemicals can modify the basic properties
of peptides, rendering the information provided far less useful.

Enhanced resolution

The team worked with partners at the Universities of Manchester and Barcelona to develop a technology that means the fluorescent chemical probes are triggered by a target molecule, or in a specific environment, which means the fluorescence only appears after they have interacted with their specific target.

This results in a higher sensitivity compared with other imaging technologies and allows it to be used in smaller concentrations – a significant advantage in clinical translation.

The technology has already been patented and now the work of Dr Vendrell and his team continues to ensure that it can have as wide a clinical use as possible. “We believe this is revolutionary because it allows us to put on a fluorescent tag, but the peptides will behave in exactly same way, so that reassures us that the information we are extracting directly correlates to the natural behaviour of peptides in the cells,” says Dr Vendrell.

As the tags allow enhanced resolution, they improve the ability of medics to assess what is happening in real time – a huge advantage once the technology is introduced to the human body. So far, the team has validated the technologies in aboratory models and animal models that resemble human disease.

Now it is engaging with the relevant agencies to begin clinical trials that will hopefully see the compounds put into humans. The technology that Dr Vendrell’s team has developed is already having an effect, with a number of labs around the world requesting it to start to study peptides in different ways.

The next step is to receive the go-ahead to use the technology in biopsy tissue, and then, eventually, in live humans, although this is likely to be a few years away. Surgeons can already take fluorescent images in the human body, a technology used most often to help them reset cancer nodules. Once permission is received to use the compounds in humans, the monitoring of the system should be relatively straightforward.

Fluorescent microscopy is currently used to see the tags, but Dr Vendrell and his team are investigating ways to make
the technology compatible with scanners already in clinical settings, such as introducing radiolabels, so that it can be
used with PET scanners.

One of the biggest advantages is that it can be applied to almost any peptide, meaning it will enhance understanding
of a wide range of diseases and processes, from cancer to the regeneration of tissue. “The impact is still yet to be
determined, but I think it is going to be very important, because already we have had very good feedback from the scientific community and we have patented it and signed licensing agreements,” says Dr Vendrell.

“Our resources here are relatively limited so we would not be able to manufacture this technology for everyone in the world who wants to use it, so it is very important for us to line up with companies who would be able to do that.”

ALL ABOUT MARC
✔ Graduated in Chemistry at the University of Barcelona in 2007
✔ Joined the Singapore Bioimaging Consortium to work with Young-Tae Chang in synthetic fluorophores for optical imaging
✔ Has over 50 publications in chemical biology and imaging, including eight international patents
✔ Research has been recognised with several international awards and fellowships
✔ These include XIII SEQT Young Investigator Award (2007), SBIC Chairman’s Prize (2010), Marie Curie Fellowship (2013).

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