An informative interview accompanied by video with Professor Silvio Aime, Head of the Molecular Imaging Center at the University of Turin (Torino) and Professor of General and Inorganic Chemistry for the Biotechnology degree course, who shares with us his insight into molecular imaging and multimodality.
Please can you outline the aims of the Centre of Molecular Biotechnologies at the University of Torino?
The Center of Molecular Biotechnology at the University of Torino was founded about 10 years ago by biologists from the Faculty of Medicine; a few chemists (our group, essentially) from the Department of Chemistry, and a few bioinformaticians from the Physics department.
The reason for founding this interdepartmental center was to join our efforts in order to tackle relevant medical needs. Therefore, for us it was a unique opportunity and we are definitely happy to have done it.
How important is molecular imaging in tackling un-met medical needs?
Molecular imaging aims to visualize molecules or molecular events that occur at the cellular level. Clearly it also allows the possibility of looking inside the biochemical pathway at the cellular level, and therefore enables us to look at the onset of diseases well before they are resolved into structural change. This is what we are currently using it for.
Ever more important, I think, is that Molecular Imaging, by allowing the visualization of the proper biomarkers that are the hallmarks of the diseases of interest, allows one to assess the efficacy of a therapeutic treatment well before we can see any structural anatomical change.
So, in the year of molecular medicine, molecular imaging really represents the level of diagnostic tool that we need in order to tackle it.
Molecular imaging is really a truly interdisciplinary science. It needs biologists in order to find biomarkers related to a specific disease. It needs chemists that will design and synthesize the proper probe in order to target this biomarker of interest. It needs imaging scientists in order to take maximum advantage of the available imaging modalities. Of course it also requires physicists and engineers to develop the scanners with the right sensitivity and specificity.
So, I think molecular imaging is the way to merge all these skills in order to tackle, in the most suitable way, the issues for early diagnosis, and for monitoring the therapeutic effect of any given treatment.
How has multimodality impacted your workflow?
I grew up with NMR and then I passed to MRI, but what I have found most exciting in the last 10 years or so is really the possibility of multimodality imaging.
To see the different ways that we have for interrogating our living systems and use the proper imaging modality for the [specific] advantages that it can give… and then to merge the information coming from the different imaging modalities – this is the most exciting possibility we have in the field.
This is what really makes molecular imaging a strong tool in the hands of the scientist, for revealing new aspects of what is recorded inside living systems.
What excites you most about the current applications of molecular imaging?
MRI is based on NMR Spectroscopy, which is the best language for talking to nature. We know how it is vital to exploit different field strengths in order to extract maximum information from the system that we are investigating.
Most people think that we just have to move to high-field in order to make the most of the information. And of course we know that moving to high-field has its drawbacks – it can be quite costly to move up any Tesla in magnetic field strength.
But at low-field, let’s say the low/intermediate field, to work at the 1 Tesla level, as in the case of this beautiful ICON system, gives us unique possibilities. Anytime we use a gadolinium-based agent or a even a paramagnetic basic agent, the best field is 1 Tesla.
So, we can show that there is a real advantage in working at 1 Tesla in comparison to, for instance, 7 or 9 Tesla, when one is using a relaxation enhancer to target a specific epitope in the region of interest.
In what ways has the field changed over time?
We have changed a lot in terms of the way we look at imaging proper design and testing in the last decade.
Until the late 90s we were essentially attracted by the development of contrast agents for MRI application and were restricted in some domains, in particular with the vascular and the extra vascular domain, because it is always very difficult to reach enough sensitivity with MRI contrast agents entering into cells.
The possibility to use complementary imaging modalities was our goal in the last 10 or so years. This changed, quite drastically, the structure of our group because we have to get users quickly used to the basic principles in order to have efficient imaging reporters for the other imaging modalities.
This, of course, definitely enriched the capability of our center and we are very pleased to have done it.
So, our students now pass from one imaging modality to another to get used to the different classes of imaging reporter agents.
What do you think the future holds for molecular imaging?
I think the future of molecular imaging is very bright. The possibility to look inside the body with high spatial resolution and to look at the biochemical processes that are related to the onset of disease, presents a beautiful scenario for translating all the terrific achievements that have come from biology and from molecular medicine.
I think that the possibilities molecular imaging continues to offer – to look in depth, inside living systems – and any developments in this direction in the forthcoming years, will make this science even more important than it is now.
Clearly we are looking towards the clinical translation of several of the achievements from the past decade to the field of clinical studies.
What barriers still need to be overcome in order to achieve these aims?
To some extent I think we are on the tip of an iceberg where the potentiality can be dramatically improved by looking at small objects, such as live cells, because in principle we always aim to go down to single cell information.
So the increase of sensitivity of the imaging probes and the imaging technology are the barriers we face.
Of course we are already in a very good position and we think that some of the molecular imaging procedures are already ready to be translated to the medical world; but the improvement in sensitivity of the imaging probes, as well as the improvement in sensitivity of the imaging scanners, are actually the barriers we have to overcome.
What are your further research plans?
We are working in collaboration with several industries and this helps us substantially with the recognition of the mathematical need, that then allows us to tackle the important programs.
I think the main direction to which we are putting our efforts is towards gaining further insight into metabolic imaging. To understand the metabolic processes that occur at a cellular level is the way to really see the functioning of cells.
Another important direction that we are pursuing deals with the development of theranostic agents that allow the clinician to simultaneously undertake diagnosis and therapy.
We seek to improve, through the use of imaging, drug delivery itself and thus give the clinician the possibility to deposit the amount of drug that is really necessary, at the targeting site, and to look at the effect of the process of release and, possibly, the effect of the drug.
At another level we want to support the surgeon to do his job better by using the protocol of molecular Imaging. This leads into the new emerging field of imaging-guided surgery, where we use the same principle of targeting molecular events at the cellular level in the surgery theater. Therefore, the surgeon can really see residual tumor cells – or a way to recognize the nerves or to recognize vessels – whereas, currently, this is very difficult.
Below: Prof. Aime shows us the University’s multimodal facilities: