[Constantin Coussios:] I first became involved with high-intensity focused ultrasound (HIFU)
in 2004, when I moved to Oxford.
One can actually focus sound in the same way as one can focus light,
so what you are dealing with is an ultrasound transducer loudspeaker, in effect,
which has got a certain shape that allows us to bend the sound
on to a specific location,
on to a region about the size of a grain of rice
at an almost arbitrary depth within the body.
We are gradually moving towards and pioneering the ability to do the drug delivery,
not with a high-powered loudspeaker,
but something that looks much closer to a diagnostic ultrasound device
-- something that is simpler, lighter, safer for the patient
and more readily available to hospital units around the world.
Where the ultrasound hits cancerous tissue,
tiny bubbles are actually created and excited by the ultrasound.
As these bubbles pulsate, they act as micro pumps that help push the drug into the tumour.
[Robert Carlisle:] One of the biggest challenges in delivering chemotherapeutic drugs is that,
when we inject them intravenously,
they immediately disperse into all our organs and tissues
and this gives us very nasty side effects.
So what we want is a much more targeted way of delivering drugs
so they get to the tumour and don't hit our normal healthy tissue.
[Constantin Coussios:] The farthest cancer cell from a blood vessel...
has been reported to be about 150 microns,
this is .15 of a millimetre.
So when delivering a drug, what you want to make sure is
that it actually exceeds .15 of a millimetre travel distance from the nearest blood vessel.
No one has ever previously demonstrated the ability to deliver drugs that far.
What we have demonstrated for the first time is that,
with the addition of ultrasound and cavitation,
we can deliver drugs as far as .2 or even .25 millimetres from the nearest blood vessel.
[Fergus Gleeson:] If you imagine a sun
and you focus it with a magnifying glass on a leaf,
it burns a hole in the leaf by concentrating the sun's rays.
Well, HIFU works in exactly the same way.
What we intend here is to raise the temperature of the body,
but not nearly enough to cause a burn,
just enough to release the drug when it's in its capsule.
[Robert Carlisle:] This drug formulation contains a very conventional and old chemotherapeutic agent
within a sphere of what we call lipid and cholesterol.
Lipid and cholesterol are essentially what is in butter
and, just like butter, the formulation we use melts in response to being heated
and loses its structure
and, in doing so, the drug is released.
[Constantin Coussios:] Typically, when the drug is injected into a patient,
less than 0.5% of that total drug dose will actually make it to the target tumour.
Using the thermal and mechanical effects of ultrasound,
the drug dose recovered can be as much as 25%.
We're about to initiate, this summer,
a first-in-man trial of ultrasound-enhanced drug delivery for cancer,
whereby patients will be treated in Oxford.
Patients who have metastatic liver disease will be given this from a sensitive liposome
and it will be non-invasively triggered using a clinical HIFU device.
[Fergus Gleeson:] Once we've managed the trial and shown it works,
then there are other drugs you might choose to put in the lipids.
And there are other tumours -- renal tumours, tumours in the abdomen, soft tissue tumours...
So it will open up a completely new branch of therapy.
[Constantin Coussios:] It is the very first time that these strategies are being tried in-man
and we are very excited.
If some of the benefits that we have been seeing in preclinical models
-- the much higher concentration of drug accumulated in the tumour,
the ability to achieve drug delivery on demand --
are actually realised in humans,
it will most probably change the face of oncology for decades to come.