A two-part upgrade for the proton accelerator

The high-intensity proton accelerator HIPA is as high-profile as it is long-serving. It started operating back in 1974 and thanks to continuing refinements it currently delivers one of the world’s most powerful proton beams, at 1.4 megawatt.

Between 2025 and 2028, HIPA is to receive an upgrade. The project called “Isotope and Muon Production using Advanced Cyclotron and Target technologies”, or IMPACT for short, consists of two parts. Firstly, “High-Intensity Muon Beams”, abbreviated as HIMB, involves remodelling part of the facility. The aim is to increase the available special elementary particles, or muons, up to one hundred times, producing an intense beam of 10 billion muons per second.

For the second part of the project, PSI aims to make an even stronger contribution to personalised cancer therapy in future, by building an improved production facility for radionuclides at HIPA. This initiative is called “Targeted Alpha Tumor Therapy and Other Oncological Solutions”, or TATTOOS for short.

The ETH Board has now put forward the overall IMPACT project as an official candidate for the Swiss Roadmap for Research Infrastructures 2023. IMPACT is a joint project of PSI, the University of Zurich and the University Hospital Zurich.

Among the other projects proposed for the roadmap by the ETH Domain, PSI is involved in two more: "EM-Frontiers", which is intended to advance electron microscopy methods, and "SDSC+", which aims to expand the Swiss Data Science Center into a decentralised national digital infrastructure.

As for IMPACT, Klaus Kirch and Roger Schibli are in charge of the project from the PSI's side. Klaus Kirch is Head of the Laboratory for Particle Physics at PSI. He describes how HIMB will improve our understanding of the universe.

Roger Schibli, Head of PSI’s Center for Pharmaceutical Sciences, explains the importance of TATTOOS for the future of cancer treatment.

Interview with Klaus Kirch

“A jewel we must treasure”

Mr Kirch, PSI’s muon facility is already one of the world’s most powerful accelerators. What’s the purpose of an upgrade?

Klaus Kirch: That’s true: our high-intensity proton accelerator HIPA is unique and unmatched worldwide. We are clearly out in front when it comes to muon production. Together with the University of Zurich, we are now planning a timely expansion of research carried out here on the PSI campus. This will allow us to maintain our leading global position over the next 20 years.

That’s a lot of superlatives.

Absolutely. HIPA is a jewel – and we must treasure it. We take it for granted that the facility runs so well, but certain components are already 45 years old. This means we are also a permanent construction site as we work to preserve the immense value of our incredible facility.

Can you describe some of the experiments performed specifically using muons?

On the one hand we use muons to research particle physics. This involves the tiniest particles and the biggest fundamental questions: What are the exact properties of the building blocks of matter, such as the proton as part of the atomic nucleus, and what precisely are the laws that govern the universe? We engage in fundamental research at the very frontier of current knowledge. To do this, we are working with highly advanced technology, which makes us very attractive to young scientists.

What exactly do you mean by highly advanced technology?

Amongst other things, we are currently developing the next generation of thin pixel detectors offering unprecedented time resolution in the picosecond range (10^-12 secs.). Requirements are extremely demanding in particle physics and the necessary systems cannot simply be bought off the shelf. So we develop and design these devices ourselves, as our research would otherwise be unable to progress. In doing so, we set completely new standards. A great deal of our successful breakthroughs in particle physics often turn up later in a simpler and more robust version in other research fields, such as detectors or specialised electronics systems.

You said particle physics was one aspect of research with muons. What’s the other?

Apart from particle physics, PSI scientists also use muons to conduct experiments in materials science. PSI has been operating a facility for muon spin rotation since as early as 1989. With this method, you place a muon in the sample material, wait for it to decay and then – after about two millionths of a second – measure the decay product. This allows the measurement of specific local properties of the materials, which no other method can provide. As things stand, we usually only send one muon after another into the material. Once the upgrade is complete, however, we want to trace the decay particles and in doing so determine their respective place of origin. If we are able to do that, we no longer need to wait for each muon. In other words: a single-lane road becomes a 12-lane highway. Or even 100 lanes! Completely different measurements would then be possible. We could measure different areas of the sample at the same time. Or measure two different samples next to each other, with exactly the same temperature, pressure, and so on.

Why perform the upgrade at this time?

We have now reached the point where there is both the demand and the necessary know-how. We could not have managed such high particle intensities before now, as we did not have the necessary detectors or data processing capabilities. The experiments generate vast quantities of measurement data. This is also interesting for the relatively new PSI research division Scientific Computing, Theory and Data, established in June 2021. And it’s wonderful to see how the researchers from these different divisions are learning and benefiting a lot from one another.

Interview with Roger Schibli

Radionuclides for personalised medicine

Mr Schibli, PSI is well known for its large research facilities. So perhaps it’s surprising to learn that PSI also produces medicines for treating tumours, known as radiopharmaceuticals. How does that fit in?

Roger Schibli: Medically established radiopharmaceuticals are produced fresh every day at hospitals or commercial radiopharmacies. At PSI, on the other hand, we produce new, experimental agents. In each case, these are drugs that carry radioactive isotopes, so-called radionuclides. In the future, we want to use the many high-energy protons from HIPA for the production of our radionuclides at PSI. This will open up production routes for new radionuclides that have never been studied before and are unparalleled in quantity and quality.

What is the current status for the use of radionuclides in cancer treatment?

The idea of using radionuclides to treat tumours dates back to the 1950s. The radioactive isotope Iodine-131 was produced since the nuclear fission of uranium was first discovered. Because iodine migrates selectively into the thyroid, it was used as one of the best forms of treatment for thyroid carcinomas till today. In the last 10 to 15 years, researchers have realised that other radionuclides could be used to treat so-called neuroendocrine tumours, cancerous growths in hormone-producing glandular tissue. In addition, the chemistry which is utilised to bind the isotopes to carrier molecules, which in turn dock with the tumour cells, was developed at the University Hospital of Basel and elsewhere.

And now?

In the last five years we have experienced a real boom in radiopharmaceuticals. The search is now on for bespoke radionuclides. As a simple example: when treating a patient with extremely small metastases, a different radionuclide is required than when treating large metastases.

Is it always about metastases?

Yes. Surgery or external irradiation is more suitable for a single cancer lesion – usually the primary tumour. Radiopharmaceuticals are the best choice when surgery and external irradiation are not an option or chemotherapy has failed. In other words, in what for many years had been considered hopeless cases. We want to develop theranostics for these patients.

What does the term theranostics mean?

Theranostics describes the combination of therapy and diagnostics. This is the new standard in radiopharmacy: the diagnostic and the therapeutic radionuclide belong in the best case to the same element, i.e. to the same atomic species. This means that they behave identically in the body. In this way, not only can we localize the metastases during diagnostics, but we can also predict which metastases will absorb a lot of the therapeutic agent and which metastases will still absorb too little. Then we can react accordingly, and that's exactly what we mean when we talk about personalized therapy.

What does the upgrade TATTOOS entail?

TATTOOS, which we are building together with the University of Zurich and the University Hospital Zurich, will be a completely new facility, and a world first. Here at PSI, the facility will include a new proton beam line as well as new targets, a mass separator and laboratories for the processing of novel radionuclides. The targets are multiple thin metal discs connected in series. When the high-energy protons hit the discs, a large number of radionuclides are produced and the discs become very hot – we are talking more than 2,000 degrees Celsius. In the process, many of the radionuclides evaporate and we can collect them. Then we isolate the radionuclides we want, using mass spectrometry and chemical separation methods.

How does mass spectrometry work?

In this process, lasers are used to ionize a specific type of isotope so that it can be separated even better. PSI is already very well positioned in terms of laser physics and also works closely with CERN in this field. We can now build on this.

When can we expect these new radiopharmaceuticals to be used in hospitals?

The development of radiopharmaceuticals, not unlike other drugs, is a lengthy process over many years. With TATTOOS, we are entering completely new territory and it will take several years and many preclinical experiments before we can test a new radiopharmaceutical in patients.

Text and interviews: Paul Scherrer Institute/Laura Hennemann

Update June 2023: On 2 June 2023, SERI published the Swiss Roadmap for Research Infrastructures with IMPACT now being on it. The roadmap is part of the ERI Dispatch 2025-2028, which the Swiss Parliament will vote on in 2024 and thus also decide on the funding of IMPACT.