One of the most exciting areas giving new hope for the treatment of solid tumours is the use of High Intensity Focused Ultrasound (HIFU) which provides a means of destroying cancerous cells within the body without the need for a major operation. This same technology can be used to break open capsules containing drugs as they pass through the body close to a tumour. The latter is sometimes referred to as targeted drug delivery because it releases drugs only at a specific point in the body where it is required to combat cancer.
We are involved in the development of such capsules.
It was not so many years ago when a diagnosis of cancer was extremely worrying for the affected patient because there were few certain cures. However in recent years there have been many improvements in the treatment of various types of cancer some invasive involving surgery, some non-invasive involving drugs and some combinations. One of the most exciting areas giving new hope for the treatment of solid tumours is the use of High Intensity Focused Ultrasound (HIFU) which provides a means of destroying cancerous cells within the body. This same technology can be used to break open drug containing capsules as they are passed through the body close to a tumour. The latter is sometimes referred to as targeted drug delivery because it releases drugs only at a specific point in the body where it is required to combat cancer.
Background to HIFU
Applications of ultrasound in medicine are well established and can be broadly divided into two domains
- the use high frequency ultrasound (around 5MHz) in medical imaging, sometimes called ultrasonic scanning. One major use of this is as a routine part of antenatal medicine to obtain an ultrasonic scan of the foetus in the womb
- at lower ultrasonic frequencies with higher energy inputs it can be used for physiotherapy, in dentistry for the descaling of teeth and to improve cutting using ultrasonic scalpels.
Diagnostic ultrasound uses a refined pulse echo technique to build up an image of internal parts of the body. It is based upon the fact that sound waves are reflected by different amounts from the interfaces between tissue, blood and bone. The high frequencies and low energies employed mean that there is no effect upon the parts of the body through which the beams pass, the effects are only felt at the focus.
It is well known that light from the sun can be focused through a lens to provide a hot focal point capable of burning paper. What is less well known is that beams of ultrasound can be focused to a point where they meet and provide again a high energy focus. If the ultrasound is of high frequency and low power as is diagnostic ultrasound and the focus is produced within the body there will be no damage at all to the body itself except at the focal point. The focus contains enough energy to destroy cells. This is the principle of HIFU and on its own it can be used to kill cancer cells. For HIFU treatment the patient lies on a bed into which is inserted a small bath of water with the part of the body to be treated touching the surface of the water. The bath contains two concentric ultrasound transducers. One transmits a low-power diagnostic beam, allowing the doctor to locate the tumour within the patient and guide the treatment; the other produces the focussed beam.
Targetted drug release
Using such a HIFU focus it is also possible to break down capsules to release drugs contained within them and this is the key to targeted drug delivery. The reason why we need targetted Drug delivery is, in simple terms, becauseit ensures that during treatment, the chemotherapy drugs get to where they are needed without harming other parts of the body. Currently chemotherapy treatments are usually given orally or intravenously and so become distributed throughout the body often lead to debilitating side effects e.g. hair loss, sickness, fatigue, depression, insomnia, and infection, to name just a few. The actual concentration where it is needed i.e. near the cancer is low.
We are trying to develop a new way of treating cancer which is more accurate and penetrative and at the same time has less or no adverse side effects. We are doing this by:
- Encapsulating the chemotherapy drug in a plastic coating (capsule/pellet)
- Inserting tiny metallic (nanometallic) particles into the capsule so that the capsule can be moved with magnets and manoeuvred into more accurate position before HIFU treatment
- To use the nanoparticles to adjust the energy required to break open the capsule when it is hit by the sound waves. Thus the cancer drug can be released from the capsule using lower power HIFU.
- Once the capsule is hit by the ultrasound wave it will disperse into the lump or tumour.This form of treatment can be used on solid or localised cancers e.g. liver, bone, breast, pancreatic, and prostate, the most common cancers.
What have we done so far?
In the last 18 months we have developed capsules containing drugs and dispersed these capsules into a gel which mimics the consistency of human tissue. These have been submitted for trials by Churchill Hospital who have the specialist HIFU equipment.
The HIFU equipment has come from Chongqing HAIFU Technology Co Ltd. in Chongqing China who are a world-leading manufacturer of non-invasive ultrasound therapeutic systems for both malignant and benign tumours. Professor Tim Mason, a specialist in sonochemistry, is based at Coventry University and is leading the research team; it was he who facilitated the import of specialist equipment through his relationship with Professor Wang of the HAIFU company who originally designed and developed the HIFU equipment in China. Professor Mason is also an Honorary Professor at Chongqing Medical School.
In May 2001 approximately 150 delegates, representing 9 countries attended a workshop in Chongqing that was the first devoted to new developments in therapeutic ultrasound. There were 45 papers presented, giving insight into the current topics of research into HIFU. Professor Mason was involved in the organisation of this event. It was only a few years after this that a team including him were involved in the acquisition and installation of a fully operational theatre instrument at the Churchill Hospital in Oxford. At the time this was the first such instrument in the western world.