Dr Maria Paula Marques and Dr Luis Batista de Carvalho from the University of Coimbra, Portugal are frequent ISIS users. Having been visiting us since 1999 they have used most of our instruments and seen a good many changes on site over the years.
Their group has two main research interests. One of them is bones, which they have investigated to help forensic scientists identify burnt remains after they have been altered by the heat. This research was featured in a previous science highlight and allowed them to assist in forensic analysis as well as in the characterisation of archaeological skeletal remains. Their other area of research is cancer. In a previous study at ISIS the team studied the changes occurring within a cell as it undergoes normal-to-cancer transition, as well as the effect of drugs on cancer cells. This fascinating research won them the 2019 ISIS - Society Impact Award .
This July the team were back again, combining their two research interests together to investigate the effect of cancer on bones using neutrons…
Metastasis is a process associated to certain types of cancer, during which an initial tumour is able to cross into the bloodstream and migrate to a completely different part of the body, where it generates a secondary tumour. While not all types of cancer are able to metastasize, those that can cause the majority of fatalities. This is one of the reasons why it is so important to catch and diagnose cancer early, so it is treated before it spreads. Also, a better understanding of the metastatic process will allow the development of improved anti-metastatic drugs. One particular symptom that often comes from metastasis is fragile bones, which become full of cavities and cracks that make them easier to break. Dr Maria Paula and her team hope to uncover the chemical and structural changes associated to metastatic lesions and so help with future treatments and pain relief.
So why use neutrons?
Normally when we talk of imaging bones the immediate response is to think of x-rays. However, while the team has also performed EXAFS (an X-Ray Absorption Spectroscopy technique) at the Diamond Light Source, the neutron data allows them to see certain gaps in the x-ray vision. While x-rays “see" mainly the heavy atoms in samples, neutrons allow the detection of lighter elements such as hydrogens. Hydrogen is especially important in biological molecules such as proteins and lipids – which are exactly the molecules that the team suspect the cancer is affecting in bone. If they can study the changes in atomic structures through both neutron and x-ray techniques, they will create a more complete picture of what is truly happening to the bones when they are affected by metastasis. Another reason this group finds neutrons useful is because they are able to probe inside delicate structures such as bones, without damaging them in any way. Which is vital, as many of their bone samples need to be returned to hospitals or museums undamaged.
The experiment itself involved 6 different bones samples, including a hip, a sternum and two rib specimens. Some of these displayed sections of cancer-affected bone as well as healthy bone. This allowed the researchers to scan different sections of the same bone fragment to compare the protein, lipid and mineral components. The experiment was also undertaken on two different neutron spectrometry instruments, MAPS and TOSCA. This allowed the team to combine the low frequency data provided by TOSCA with high sensitivity with that at high frequency from MAPs, which together will build a full picture of the analysed samples.
The hope is that an improved understanding of the chemical and structural changes prompted by cancer in bones, can help inform future treatments, both anti-metastatic and pain-controlling, improving quality of life as well as a possible steppingstone to creating a cure. This research is still underway, but we greatly look forward to seeing the results they produce!