Antiprotons: effects on biological matter and evaluation as a novel radiotherapy

After surgery, radiation treatments are the most widely used and successful way to cure cancers. However, modern radiotherapy plans often cause severe side-effects to the patient and the overall success rate is still only moderate. Therefore there is a need to research new ways of delivering radiotherapies in order to inform and improve new treatments in the future.Radiotherapy works by killing cancer cells - usually by breaking the DNA in those cells. If the damage is so severe that the cells cannot repair it, the cells die. A lot of the research into radiotherapy is aimed at understanding how cells respond to radiations of different types and doses.One reason why radiotherapy results in side-effects is because healthy cells are damaged, or killed, as well as cancerous ones. Therefore considerable efforts have been made to minimize these effects and to focus the destructive power of radiation on tumour cells. This has been achieved, to some extent, with X-rays by irradiating the patient from multiple external sites. An alternative, and very promising, approach is the use of ion beams in place of x-rays. There are already numerous proton treatment facilities worldwide (including one in the UK) and centres using heavier ions (eg carbon) are now being brought into operation.The big advantage of ion beams is due to the way they deposit their energy in tissue. When an X-ray beam enters a person, energy is deposited immediately upon entry, thus causing damage. In contrast, ion beams can pass several centimeters through tissue before depositing the bulk of their energy. By manipulation of the physical properties of the ion beam, the depth at which ion beams deposit their energy can be controlled and made to correspond to the site of the tumour. Thus the bulk of this type of radiation's destructive power is concentrated in the cells which we wish to destroy. The results from ion beam irradiation are impressive, with improved clear-up rates and decreased side-effects.A further improvement on ion beams, may be to use antiprotons. Antiprotons will be familiar to any reader of science fiction - usually as the means of propulsion of interstellar starships or in a fearsome and destructive weapons systems. However, antiprotons can be produced here on earth, contained, controlled and used in experiments. Like their regular matter counterparts, protons, they can pass through material for several centimeters before depositing their energy. Their potential advantage arises from the fact that when an antiproton meets a proton, the two particles annihilate each other (according to Einstein's famous equation E=mc2) releasing lots of energy.A group of scientists at the European Centre for Nuclear Research (CERN) in Switzerland have begun experiments to see if antiprotons can be used in cancer therapies. This group (the ACE collaboration) have shown that antiprotons kill cells approximately four time better than protons. However, before antiprotons can be considered a viable possibility in cancer radiotherapy, considerable extra scientific work is required.In 2008, the applicants joined the ACE collaboration and carried out an experiment at CERN to investigate the effects of antiprotons on cultured human cells. They showed that antiprotons cause damage to the DNA in these cells and that the more antiprotons the cells are exposed to, the more DNA damage is caused. In addition, they demonstrated that media from irradiated cells can cause DNA damage responses in non-irradiated cells. This phenomenon, the so-called bystander effect, is well documented with other types of radiation, but has not previously been shown with antiproton irradiation.The applicants now seek funding to return to CERN in autumn 2009, in order to continue these experiments. This year they hope to learn more about the bystander effect resulting from antiproton irradiation, including quantifying the magnitude of these effects.

Who will benefit from this research? 1. Cancer patients (long term, ie 10+ years): They will benefit from, potentially, a new form of cancer therapy. This cannot be developed without initial, basic research of this nature. 2. Scientists interested in the effects of antimatter on complex systems (medium term, ie 5-10 years) 3. Scientists working on the effects of radiation on cells, especially the by-stander effect (short-medium term, ie 1-5 years) 4. The ACE collaboration at CERN (short-medium term) 5. The applicants (short term, ie 6-12 months) How will they benefit from this research? 1. From (potentially) a new, effective, safer form of cancer therapy which will be particularly useful for cases which are currently difficult to treat with conventional radio- or chemotherapies. 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 2009 run. 5. If this travel grant is not funded, it is unlikely that we will be able to take part in the ACE collaboration's 2009 run. 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 to ensure that they have the opportunity to benefit from this research? 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. 5. Through the publication of the data in a timely fashion and the application for further funding to support this area of research. In addition, to disseminate the information to the wider public, we will work with the Press and Publicity directorate at Queen's University, Belfast in order to promote the results of published work in the public media. The University 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 considerable success in this endeavour.