Ion Beam Radiotherapies: Comparison of Protons, Antiprotons and Heavier Ions

Radiation can cause cancer, but it can also be used to cure the disease. Indeed radiotherapy is more widely used than chemotherapy. It works by breaking DNA molecules in cells, which causes these cells to die. However, radiotherapy has a major problem: it isn't a very selective method and often damages healthy tissue, as well as killing the tumour. So a lot of work has gone into finding ways to minimise this damage, while making sure that the treatment still destroys the tumour.One way to improve the targeting of radiation is to use beams of ions (instead of x-rays, which are normally used). This works because ions do not lose much energy when they first enter the body (unlike x-rays which start depositing energy, and therefore causing damage, the moment they enter you). Instead they lose most of their energy at a precise distance into the body, at the so-called Bragg peak. The position of this Bragg peak depends on how fast the ions are travelling and what type of ions they are. So the position can be controlled such that it corresponds to the tumour. This enables the destructive power of the radiation to be focussed into the tumour, largely sparing surrounding, healthy tissues.Facilities which use hydrogen ions (protons) to treat cancer patients are in use in many countries worldwide. The results are impressive with improved treatment success and reduced side-effects. The NHS has recognised this potential and plans to build a new proton facility.However, the most modern facilities use ions from heavier elements such as carbon. It has even been suggested that ions of antimatter could be used. Although this sounds like something from a science fiction story, anti-protons can be made here on earth. They behave a lot like regular protons, passing through matter and depositing most of their energy at a Bragg peak. However, when an antiproton and a proton meet, they annihilate each other releasing even more energy. So they have the potential to be more effective than protons, because of this additional energy release.We have initiated a programme of experiments to compare how protons, carbon ions and antiprotons interact with living matter. We want to compare and contrast these different forms of radiation. In particular, we want to learn how they damage DNA in the cell. We have already learned quite a bit about how antiprotons damage cellular DNA. So we want to complete these experiments and extend them to protons and carbon ions. We will see if these types of radiation cause radical alterations to the chromosomes (the structures in cells which contain the DNA). We will see if the irradiated cells can repair their damaged DNA, and how fast they can do it. This is important because in radiotherapy we want to cause non-repairable damage. When irreparable damage occurs, cells often commit suicide in a special type of cell death called apoptosis. We will also look at the cells' chromosomes to see if any gross changes in structure have occurred.Although we can learn a lot from intact cells, they are sometimes just too complex. So we plan to use a special type of DNA molecule called plasmids because there is a straightforward method to see if these have been broken on one strand, both strands or in lots of places. We can also use this method to quantify the damage and find out how much radiation is required for a particular level of damage. So we should be able to compare the radiations.However, we can't do these experiments in the UK. There is only one source of antiprotons at sufficient energy in the world - at CERN in Geneva. Nor is there a source of carbon ions at clinically relevant energies. So for this we plan to travel to Catania (Italy) to do these experiments.The results will be of interest to oncologists looking at potential, novel cancer treatments, but also to a wide range of scientists who want to understand how radiation interacts with living matter.

Who will benefit from this research? 1. Cancer patients (long term, ie 15+ years for the antiproton work; 5+ years for the proton and carbon ion work) 2. Scientists interested in the effects of antimatter on complex systems (medium term, ie 5-10 years) 3. Scientists working on the effects of ion beam radiation on cells, especially the by-stander effect, hypoxic effects and fundamental molecular mechanisms of damage (short-medium term, ie 1-5 years) 4. The ACE collaboration at CERN and heavy ion facility scientists (short-medium term) 5. The applicants (short term, ie 6-12 months) How? 1. A better understanding of how ion beams interact with cells and biomolecules at therapeutically relevant energies may improve treatment protocols and/or planning. They may also benefit from a new, effective, safer forms of cancer therapy which will be particularly useful for cases which are currently difficult to treat with conventional radio- or chemotherapies. This cannot be developed without initial, basic research of this nature. There is also a vital need to compare and contrast different forms of (potential) therapy - in this case carbon ions versus antiprotons. This will inform decision making about which types of novel radiotherapy to invest in. This has clear implications for the quality of life of these individuals and their health and wellbeing. 2 and 3. From the additional knowledge which we will obtain. This will inform their own work - especially experimental design and data interpretation. 4. We will bring skills and expertise to the ACE collaboration which would not, otherwise, be available. This means that we will bring our own experiments (as outlined in the case for support) which are unique within the collaboration. Furthermore, we will contribute to discussions on all the experiments being carried out during the 2010 run. We will translate successful experiments from CERN to the heavy ion facility. Thus, scientists located there will have the benefit of our prior expertise which will be applied in experiments with a high chance of success. Our work will demonstrate that both facilities have value beyond pure science and that they contribute to the enhancement of human health and well-being. 5. If this travel grant is not funded, it is unlikely that we will be able to take part in the ACE collaboration's 2010 run or extend our work into other forms of ion beam radiation. Taking part will enable us to advance our own work in this area, inform the work in our various labs in Belfast and to publish the data in high quality journals. What will be done? 1. From publication of the work in peer-reviewed journals and from presentation of the work at oncology and radiobiology conferences. This should accelerate any translational research arising from our work. 2 and 3. From publication and from presentation of the work at Physics conferences. 4. Through the completion of various reports, including those which will contribute to the ACE collaboration's bids for continuing access to beamtime at CERN and through presentation of the work (combined with discussion of future experimental plans) at the collaboration's planning meetings. We will also co-publish with other members of the ACE collaboration and heavy ion beamline scientists. 5. Through the publication of the data in a timely fashion and the application for further funding to support this area of research. To disseminate the information to the public, we will work with the Press and Publicity directorate at QUB in order to promote the results of published work in the media. QUB makes considerable efforts to promote the work of its staff - both in the Northern Ireland press, as well as UK and Irish outlets. Since this project has a number of elements which are likely to be exciting to the general public (ie radiation, antimatter, cancer therapy), we expect success.