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Science with a medical PET cyclotron

18 March 2016

Medical PET cyclotrons can be used for multidisciplinary research.

Résumé

Faire de la recherche avec un cyclotron PET médical

Au-delà de la production courante de radio-isotopes pour l’imagerie médicale, les cyclotrons PET compacts peuvent être au cœur d’installations de recherche multidisciplinaires. C’est le cas au laboratoire cyclotron de Berne (BTL), conçu pour une utilisation de l’accélérateur dans des buts scientifiques, parallèlement à la production de radio-isotopes. Au fil des années, l’installation est devenue le principal instrument pour toute une série d’activités de recherche auxquelles participent des équipes de physiciens, de chimistes, de pharmaciens et de biologistes.

Particle accelerators are fundamental instruments in modern medicine, where they are used to study the human body and to detect and cure its diseases. Instrumentation issued by fundamental research in physics is very common in hospitals. This includes positron emission tomography (PET) and cancer hadrontherapy.

To match the needs of a continuously evolving field and to fulfil the stringent requirements of hospital-based installations, specific particle accelerators have been developed in recent years. In particular, modern medical cyclotrons devoted to proton cancer treatments and to the production of radioisotopes for diagnostics and therapy are compact, user-friendly, affordable and able to ensure very high performance.

Medical PET cyclotrons usually run during the night or early in the morning, for the production of radiotracers that will be used for imaging. Their beams, featuring about 20 MeV energy and currents of the order of 100 μA, are in principle available for other purposes during the daytime. This represents an opportunity to exploit the science potential of these accelerators well beyond medical-imaging applications. In particular, they can be optimised to produce beams in the picoampere and nanoampere range, opening the way to nuclear and detector physics, material science, radiation biophysics, and radiation-protection research.

On the other hand, to perform cutting-edge multidisciplinary research, beams of variable shape and intensity must be available, together with the possibility to access the beam area. This cannot be realised in standard medical PET cyclotron set-ups, where severe access limitations occur due to radiation-protection issues. Furthermore, the targets for the production of PET radioisotopes are directly mounted on the cyclotron right after extraction, with consequent limitations in the use of the beams. To overcome these problems, medical PET cyclotrons can be equipped with a transport line leading the beam to a second bunker, which can always be accessible for scientific activities.

The Bern cyclotron laboratory

The Bern medical PET cyclotron laboratory was conceived to use the accelerator for scientific purposes in parallel with radioisotope production. It is situated in the campus of the Inselspital, the Bern University hospital, and has been in operation since 2013. The heart of the facility consists of an 18 MeV cyclotron providing single or dual beams of H ions. A maximum extracted current of 150 μA is obtained by stripping the negative ions. Targets can be located in eight different out-ports. Four of them are used for fluorine-18 production, one is equipped with a solid target station, and one is connected to a 6 m-long beam transfer line (BTL). The accelerator is located inside a bunker, while a second bunker with independent access hosts the BTL and is fully dedicated to research. The beam optics of the BTL is realised by one horizontal and one vertical steering magnet, together with two quadrupole doublets, one in the cyclotron bunker and the other in the research area. A neutron shutter prevents neutrons from entering the research bunker during routine production, avoiding radiation damage to scientific instrumentation. The BTL, rather unusually for a hospital cyclotron, represents the pillar of this facility. Although initially more expensive than a standard PET cyclotron facility, this solution ensures complete exploitation of the accelerator beam time and allows for synergy among academic, clinical and industrial partners.

Multidisciplinary research activities

The Bern facility carries out full, multidisciplinary research activities by a team of physicists, chemists, pharmacists and biologists. The BTL and the related physics laboratory have so far been the main instrument for carrying out research on particle detectors, accelerator physics, radiation protection, and novel radioisotopes for diagnostics and therapy.

To reach beam currents down to the picoampere range, a specific method was developed based on tuning the ion source, the radiofrequency and the current in the main coil. These currents are far below those employed for radioisotope production, and PET cyclotrons are not equipped with sensitive enough instrumentation. A novel compact-profile monitor detector was conceived and built to measure, control and use these low-intensity beams. A scintillating fibre crossing the beam produces light that can be collected to measure its profile. Specific doped-silica scintillating fibres were produced in collaboration with the Institute of Applied Physics (IAP) in Bern. A wide-intensity-range beam-monitoring detector was realised, able to span currents from 1 pA to 20 μA. The versatility of the instrument attracted the interest of industry, becoming a spin-off of the research activity. Moreover, the beam monitor was used to measure the transverse beam emittance of cyclotrons, opening the way to further accelerator-physics developments.

The large amount of daily produced fluorine-18 requires a complex radiation-protection monitoring system consisting of about 40 detectors. Besides γ and neutron monitoring, special care is paid to air contamination – a potential danger for workers and the population. This system is both a safety and research tool. Radioactivity induced in the air by proton and neutron beams was studied and the produced activity measured. The results were in good agreement with calculations based on excitation functions, and can be used for the assessment of radioactivity induced in air by proton and neutron beams in the energy range of PET cyclotrons. A direct application of this study is the assessment of radiation protection for scientific activities requiring beam extraction into air.

Another distinctive feature of the Bern cyclotron is its radio-pharmacy, conceived to bring together industrial production for medicine and scientific research. It features three Good Manufacturing Practice (GMP)-qualified laboratories, among which one is fully devoted to research. The existence of this laboratory and of the BTL brought together physicists and radiochemists of the University of Bern and of the Paul Scherrer Institute (PSI), triggering a multidisciplinary project funded by the Swiss National Science Foundation (SNSF). Scandium-43 is proposed as a novel PET radioisotope, having nearly ideal nuclear-decay properties for PET. Furthermore, scandium is suitable for theranostics (combined diagnostics and therapy). The same biomolecule can in fact be labelled with a positron-emitting isotope for imaging and a β one for cancer therapy. Advances in nuclear medicine will only be possible if suitable quantities of scandium-43 are available. The goal of the project is to produce clinically relevant amounts of this radioisotope with a quality appropriate for clinical trials.

The results described above represent examples of the wide spectrum of research activities that can be pursued at the Bern facility. Several other fields can be addressed, such as the study of materials by PIXE and PIGE ion-beam analysis, irradiation of biological samples, and investigation of the radiation hardness of scientific instrumentation.

The organisation of a facility of this kind naturally triggers national and international collaborations. The 12th workshop of the European Cyclotron Network (CYCLEUR) will take place in Bern on 23–24 June 2016, to bring together international experts. Last but not least, students and young researchers can profit from unique training opportunities in a stimulating, multidisciplinary environment, to move towards further advances in the application of particle-physics technologies.

• For further reading, visit arxiv.org/abs/1601.06820.

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