The start-up Positrigo uses findings from particle physics for the early diagnosis of Alzheimer's disease

PET scanner in compact format

Positron emission tomography (PET) helps medical doctors to detect cancer and many other diseases. A team of researchers led by ETH Professor Günther Dissertori is working on a new generation of PET scanners that could in future be of great use in pharmacological research and in the treatment of Alzheimer's patients. The technical innovation is based, among other things, on fundamental research at CERN.

The first PET scanners were developed in the 1970s. Researchers from the European Particle Physics Laboratory CERN and the Cantonal Hospital of Geneva were among those involved in the further development of the technology. Since then, the medical diagnostic devices have provided valuable services, particularly in cancer diagnostics. For around twenty years now, PET scanners have been combined with computer (CT) or magnetic resonance tomography (MRT) in clinical practice. These combined devices are particularly powerful because they combine the information from PET scanners on metabolic processes with high-resolution CT or MRI data on anatomy.
CERN technology in the service of cancer medicine

"The PET scanner is full of modern physics", says ETH Professor Günther Dissertori, "it is based on radioactive beta decay, on the Einstein formula E = mc2, but also on the annihilation of matter and antimatter". Günther Dissertori is an expert on elementary particles. With his research team, he is a major contributor to the CMS experiment, one of the four large experiments that have been running at the large CERN particle accelerator since 2010. This experiment investigates the elementary particles created by the collision of protons. To do this, particle physicists use a detector that consists of shells like an onion. Each of these shells can detect certain types of elementary particles.

One of the shells is the electromagnetic crystal detector. It consists of about 80,000 artificial crystals. If a light particle (photon) hits one of these crystals, it triggers a flash of light that can be detected by photosensors. The crystal detector at CERN therefore measures photons that are produced in proton-proton collisions. "This is exactly the technology we use in the PET scanner," says Dissertori. When patients are examined with a PET scanner, they are given a low-level radioactive substance ("tracer"). During radioactive beta-plus decay, this tracer releases positrons (antiparticles of electrons), which annihilate in the body with electrons, producing two oppositely directed gamma photons (according to Einstein's formula, both photons have the energy of an electron/positron, namely 511 kilo electron volts). The crystal detector of the PET scanner can detect these photon pairs and determine their origin. In this way, researchers can reconstruct areas with tracer accumulations and derive valuable information about the metabolic processes in the patient's body, for example.
Visualize metabolic processes practically in real time

The huge research devices developed for basic research at CERN thus provide a blueprint for the construction of medical diagnostic equipment. Against this background, it is not surprising that particle physicist Günther Dissertori has been using the knowledge gained at CERN for medical applications for around ten years. One result of this work is the prototype of a novel preclinical PET scanner called SAFIR (short for: Small Animal Fast Insert for MRI). The innovation of the new scanner is its speed: in contrast to older PET scanners, it can detect more photons per unit of time, therefore process a higher rate of radioactive decay and display dynamic processes in experimental animals such as mice or rats almost in real time.

SAFIR was developed in collaboration with the pharmacologist Prof. Bruno Weber (University of Zurich) for preclinical research. The scientists use it to study, among other things, the blood flow and oxygen distribution in the brain of laboratory animals. The PET scanner, which is unique worldwide, allows these processes to be measured over time. The prototype, completed in 2019, consists of almost 3000 crystals. In addition to a spatial resolution of just under 2 mm, it achieves a temporal coincidence resolution of 194 picoseconds and enables image reconstruction within seconds - a record value. "For practical application in PET/MR devices, it is significant that our PET scanner works perfectly despite the strong magnetic fields of the MRT," says Dissertori, underlining one of the advantages of the prototype.
Early detection of Alzheimer's disease

PET scanners promise great potential not only in research, but also in the diagnosis and therapy of Alzheimer's disease. The scanners are already the most reliable method for detecting amyloid plaques. These are the protein deposits associated with the destruction of brain cells of Alzheimer's patients, which can be detected many years before the first symptoms of the disease appear. If the deposits can be detected with screening scans, people could possibly be treated before the onset of the disease. The Alzheimer's drugs that are currently being developed could be given at an early stage of the disease thanks to preventive diagnostics - a time when they might be particularly effective.

"If we want to make preventive scans available to a broad population, we need smaller and cheaper scanners than those currently available," says ETH researcher Dissertori. Based on an idea by Prof. B. Weber and Prof. em. Alfred Buck (former Nuclear Medicine, Zurich University Hospital), Jannis Fischer and Max Ahnen, two former doctoral students at the Institute for Particle and Astrophysics, have developed a compact scanner. It looks similar to the hood of a hairdresser's chair and is therefore considerably smaller than the room-filling full-body scanners that have been used up to now. With the start-up Positrigo, founded in 2018, they want to bring the novel PET scanner to market. The aim is to reduce the costs of a PET scan from the current 3000 to 4000 Fr. by a factor of 10. At the moment, the young entrepreneurs are about to conclude a first round of investments, which should enable the commercialization of the device. The first clinical studies are planned to start this year. These are the prerequisites for using the medical device on patients.
Track tumor destruction in detail

Günther Dissertori is a scientist at ETH, and he personally has no plans to become an entrepreneur. That is "another world", the world of business plans, contracts and market analyses, says Dissertori. But even if Dissertori himself remains true to science – the applications that emerge from this science continue to make new applications possible. For example, in the future compact PET scanners could be used in hospitals to examine the brains of vulnerable patients in intensive care units. Another application aims to improve proton therapy. Here, the PET scanner would be used to enable doctors to assess and improve the precision of tumour destruction using proton radiation while treatment is still in progress. Corresponding research projects led by Prof. Dissertori and financed by the Swiss National Science Foundation will start in autumn 2020 at the CHUV University Hospital (Vaud) and the Proton Therapy Centre of the Paul Scherrer Institute (Villigen/AG).

Author: Benedikt Vogel