I was invited to talk about the metabolic imaging technique that we’ve been developing over the last eight or nine years; it’s a new way of doing metabolic imaging with magnetic resonance.

So magnetic resonance is a very insensitive method and traditionally we use MRI to image tissue water protons.

Water protons are very abundant in tissues and protons are very sensitive to MR detection so we can generate images of tissue anatomy.

Metabolic imaging with MR has been around since the 1970s but the problem has been a lack of sensitivity.

So these metabolites are present in about 10,000-fold lower concentration than tissue water protons.

We can detect them; we can’t image them except at relatively low resolution.

Moreover, if you get a picture, a profile, of the metabolites in tissue that doesn’t tell you anything about flux or turnover.

If you want to understand how something works you need to see it move.

So in metabolic imaging the way we do that is to introduce a labelled metabolite, so carbon-13, for example.

You can inject the carbon-13 labelled molecule and you can detect signal from those molecules.

The problem again is sensitivity.

Carbon-13 is even less sensitive to detection than protons.

So we can’t image with carbon-13 except at very, very low resolution and time resolution is not very good.

The technique that we’ve been working on, in collaboration with GE Healthcare for the last eight or nine years or so, is a technique that increases sensitivity in the experiment by more than 10,000-fold.

So now we can do metabolic imaging in the way that has never been possible before.

What we’ve been concentrating on is to use this technique to detect treatment response, to guide therapy.

Everybody is familiar with the concept of personalised medicine, that no two patients’ tumours are the same, they differ genetically, they’ll respond differently to different drugs.

Now, you can genetically profile those tumours, that may tell you which drugs are going to work well in those tumours.

So our approach is to image very early after treatment.

So you treat the patient and then we’re aiming within 12-24 hours, maybe, to see whether the drug has actually hit its target.

That has really been the focus of our research so that you can guide therapy more effectively.

Will this displace FDG?

I wouldn’t say that, I think it’s complementary to FDG.

The limitation of the technique is that... so, if I explain a little bit about the physics of how it works.

In a magnetic resonance experiment you’re looking at a very weak interaction between a nuclear spin and a magnetic field.

What we do, part of this technique, is to polarise the spins so they give more signal.

Now, in order to do that, we take the sample down to a very, very low temperature, a fraction of a degree above absolute zero or about a degree above absolute zero, and play a trick which we don’t need to go into.

But essentially that polarises the spins and this gives us a massive gain in sensitivity.

Now, the breakthrough in this field came maybe ten years, or more than ten years, ago now where Klaes Golman and Jan Henrik Ardenkjaer-Larsen working then in Amersham, subsequently with GE Healthcare, realised that you could warm the sample up extremely quickly and retain this polarisation, albeit for a relatively short period of time.

So the half-life of the polarisation in the molecule that we used mainly is about 30 seconds which means when you inject it you’ve got to image, do everything, within a few minutes.

Now, that’s a challenge but it has already been done clinically.

So the first clinical trial has already happened and we hope to do these studies in Cambridge later this year.

So that’s the difficulty.

Now, what that means is because the signal has got such a short lifetime, you have a relatively restricted field of view.

So with FDG-PET you can do whole body imaging; this technique would be challenging to do in a whole body way so if you wanted to look for metastasis then FDG is a great way to do that.

This technique would not be a great way to do that but it is good.

So the key advantage, well there are two key advantages over FDG-PET, one, there’s no ionising radiation so you could contemplate using it in a repeat fashion – image the patient, treat them and then image again.

The other, it works in tumours where FDG doesn’t work terribly well so, for example, in glioblastoma, in prostate.

The first clinical trial was done actually in prostate.

Now, the problem in prostate with FDG is you get a lot of signal from the adjacent bladder and the prostate is not particularly avid for FDG either.

So I see them as complementary.

Really what’s going to happen in the next few years, PET-MR machines are already out there in the clinic, we plan to put this technique on to PET-MR and use multiparametric imaging, so gather as much information as you can in as short a time as possible by adding together different...

You’ve got many contrast mechanisms with MRI, you add in radionuclide imaging and then this new metabolic imaging, you can ask more specific questions.

If you understand mechanism then you can ask much more specific questions about the way the tumour behaves, what type of tumour it is.