The probability of being diagnosed with cancer increases significantly with age. Researchers at PSI are improving proton therapy, developing groundbreaking radiopharmaceuticals and a novel breast cancer imaging technique, and analysing what happens at the atomic level during chemotherapy.
The human rib cage rises and falls approximately 15 times per minute as we breathe. The same goes for the patient resting on a couch in the Center for Proton Therapy at PSI. She is here to receive radiation therapy for her lung tumour, and the motion caused by breathing presents a challenge. PSI researchers have developed a new method to ensure that the tumour is nevertheless always targeted with pinpoint accuracy.
Proton therapy at PSI is unique in Switzerland and has a history spanning more than 40 years. It represents an important complement to traditional radiation therapy in hospitals: the accelerated protons can be directed with extreme precision. This offers better protection for healthy tissue. And that’s precisely why every millimetre counts.
Custom-tailored proton therapy
The Swiss Cancer League estimates that there are currently around 450,000 cancer survivors in Switzerland. The patient at the Center for Proton Therapy hopes to join their number. To target her tumour optimally despite her breathing movements, the PSI researchers are using two methods. First, a narrow proton beam scans the tumour in all three dimensions – not just once but multiple times, each with a lower dose. This way, small changes in position during individual scans have less of an impact. Second, special cameras track the patient’s breathing. Radiation is only administered during the brief period of rest after exhalation.
An ongoing project at the Center for Proton Therapy goes a step further and addresses tumours in all regions of the body. Proton therapy is administered in numerous individual sessions, typically spread over several weeks. During this time, the tumour can shift or change shape, or there can be alterations in the intervening tissue. To cope with this, medical physicist Francesca Albertini and her team have developed a new treatment plan, which they have already successfully applied to patients with tumours in the skull: Daily Adaptive Proton Therapy, or DAPT for short. Each day of treatment begins with a low-dose computed tomography (CT) scan, which is used to determine the optimal radiation dose. The significant gain in precision more than offsets the additional radiation dose from the CT scan, explains Albertini: “In many cases, the DAPT plan can reduce the dose to sensitive structures by about ten to fifteen percent compared with the previous method. This can make a big difference for the patient.” The researchers have largely automated the process, so that each session only takes a few minutes longer overall. Next, they will test DAPT on tumours in other parts of the body, such as the abdomen.
Piggybacking to the tumour cells
Cutting-edge cancer treatment methods are also being investigated at the PSI Center for Radiopharmaceutical Sciences. Radiopharmaceuticals are used when cancer has already spread and formed metastases. While chemotherapy attacks all rapidly dividing cells in the body – including healthy ones – radiopharmaceuticals act more selectively and thus place less stress on the body.
A radiopharmaceutical consists of a radionuclide – an atom that emits ionising radiation – and a molecule that binds specifically to the tumour cells. Initially, a radionuclide is selected that emits gamma radiation, for diagnostic purposes. The actual treatment is then carried out using a closely related radionuclide that emits a suitable form of beta radiation. Unlike gamma radiation, this has a shorter range of only a few millimetres, but it is significantly more intense. This means that it specifically targets and destroys the tumour cells to which the radiopharmaceutical binds rather than the surrounding healthy tissue.
This principle has been established for several decades in the treatment of thyroid cancer, using radionuclides of the element iodine, which the thyroid gland naturally absorbs. “Unfortunately, not every organ affected by cancer has a natural affinity for a suitable element,” says Roger Schibli, head of the Center for Radiopharmaceutical Sciences. For this reason, PSI researchers are developing molecules known as ligands, which bind specifically to the respective tumour cells. The researchers then attach the radionuclide to the ligand, which carries it piggyback-style to its target. A substance developed in Cristina Müller’s research group, which utilises the radionuclide terbium-161, uses this approach to destroy even micrometastases, down to individual tumour cells, with remarkable effectiveness.
PSI is planning to build a new facility to ensure that significantly larger quantities of a wide variety of radionuclides are available in the future. Construction of TATTOOS (Targeted Alpha Tumour Therapy and Other Oncological Solutions) will begin in 2029. This is part of the major PSI upgrade project IMPACT (Isotope and Muon Production with Advanced Cyclotron and Target Technologies). “TATTOOS will open up entirely new possibilities,” says Cristina Müller. “In the future, we will investigate many more radionuclides for the treatment of various types of cancer, enabling more effective therapies while simultaneously protecting healthy organs.” This will benefit older people in particular, as well as those who have already received prior treatment, since their bodies are often less able to tolerate demanding therapies.
The long-term goal of radiopharmacy is personalised treatment, with a suitable radiopharmaceutical for each type of cancer, every stage of the disease and the individual condition of the patient. TATTOOS will enable researchers to take a major step in that direction.
More precise mammography
But the best approach is to detect cancer early on. Marco Stampanoni and his team at the PSI Center for Photon Science are working on the early detection of breast cancer. Around 6,800 women in Switzerland are diagnosed with this disease every year. The mammography technique commonly used today measures the absorption of X-rays by tissue. Tissue nodules and calcifications, which can be precancerous, appear as bright spots. The images are not perfect, however: nearly half of all suspected cases turn out to be false alarms during the subsequent biopsy. Conversely, one in five real tumours goes undetected.
Stampanoni’s research group uses a technique called grating interferometry. It is based on information obtained not only from the absorption but also from the refraction and scattering of radiation by the tissue. This leads to significantly sharper images with higher contrast. “Small objects, in particular, can be measured precisely – even in soft tissues that would otherwise remain invisible,” says Stampanoni. “It may even be possible to tell from the scattering pattern whether a change is benign or malignant.”
In the long term, the method should enable precise three-dimensional examinations without the need for painful breast compression. And grating interferometry could also be helpful in other types of cancer, such as lung cancer, because the alveoli affected scatter X-rays differently than in a healthy person.
The molecules of chemotherapy
Last but not least, PSI researchers are also working on improving conventional chemotherapy. A team led by Michel Steinmetz, interim head of the PSI Center for Life Sciences, has examined proteins known as tubulins with atomic precision using imaging techniques such as X-ray crystallography at PSI’s Swiss Light Source SLS. Tubulins are the cellular molecules to which most cancer drugs bind.
Among other things, the researchers succeeded in identifying numerous new so called binding pockets and precisely characterising others that were previously known. The active substances nestle into these tubulin pockets. The more precisely they fit, the longer they adhere and the more effective they are. “And the more precisely we know the structure of the binding pockets, the more accurately we can design new drugs that bind optimally,” says Steinmetz.
A research group led by Jörg Standfuss, who works with Steinmetz at the PSI Center for Life Sciences, has also used the X-ray free-electron laser SwissFEL at PSI to measure to within 100 femtoseconds – that’s one tenth of a trillionth of a second – how the drug and binding pocket deform when they separate. This is particularly helpful for improving novel photoactive drugs. These are medications that can be switched on and off by a pulse of light – giving them the potential to make chemotherapy significantly gentler.
From Francesca Albertini to Jörg Standfuss – they are all united by the patience and passion with which they have developed and refined their methods over many years. Together, they share the goal of taking the fear out of cancer
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