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Increasing Radiopharmaceutical Production with Cyclotrons

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cyclotron, portugal, radiopharmaceuticals

One of Portugal’s cyclotrons is generating radioisotopes to create radiopharmaceuticals for use around the world. (Photo: A. Abrunhosa/University of Coimbra) 

Twelve years ago, Portugal’s University of Coimbra invested in the country’s first cyclotron, a particle accelerator to produce radioisotopes for medical drugs known as radiopharmaceuticals. Radiopharmaceuticals are critical in diagnosing and treating cancer as well as brain and cardiovascular diseases. The introduction of the machine meant radiopharmaceuticals could be produced domestically and also supply the region. Today, Portugal operates three cyclotrons — two in Coimbra and one in Porto — which provide life-saving radiopharmaceuticals to the Iberian Peninsula, the east of France and parts of North Africa. 

The expansion of cyclotron technology over the last decade is not a story unique to Portugal. There are now over 1,200 cyclotrons in operation worldwide, producing important radionuclides and increasing the availability of nuclear medicine — ultimately providing better and more effective diagnosis.  

“Cyclotrons have changed the course of radiopharmaceuticals over the last 30 years,” said Amirreza Jalilian, a radioisotope and radiopharmaceutical chemist at the IAEA. Unlike nuclear research reactors, where radiopharmaceuticals have traditionally been produced, cyclotrons do not use a radioactive source, are easier to install and operate and can be set up directly in hospitals.  

Globally, between 10 and 12 per cent of radiopharmaceuticals are produced in cyclotrons, but the demand for cyclotrons is increasing as more of the radionuclides they produce are used in research, diagnosis and treatment in a range of life-threatening diseases such as cancer, Parkinson’s, Alzheimer’s and insomnia. 

Jalilian is a co-author of a recently published IAEA report, Alternative Radionuclide Production with a Cyclotron, which lists a variety of radionuclides that can be produced with cyclotrons. The document complements the IAEA Database of Cyclotrons for Radionuclide Production, acting as an accessible a catalogue for policy makers, researchers, companies and students as well as technical experts to gain an overview of the types of radionuclides these machines can produce and how they are beneficial in nuclear medicine, patient care and treatment.  

“In Portugal, our cyclotrons are paving the way for better diagnosis, treatment, research and development by providing a new direct way of producing some radionuclides such as gallium-68,” said Antero Abrunhosa, Director of the Institute for Nuclear Sciences Applied to Health at the University of Coimbra. “We are actively involved in research and development to make sure we meet current and future demand for radionuclides and radiopharmaceuticals for diagnostic applications.”

The many uses of cyclotrons

The radioisotopes in radiopharmaceuticals are commonly used to produce images of organs or tissues, to detect diseases and help visualise the growth and shrinking of tumours.  

The most prevailing radioisotopes produced through cyclotrons are those that have short half-lives, meaning they lose much of their radioactivity within a few hours and are therefore not suitable for long transport times. These include fluorine-18, carbon-11, oxygen-15 and nitrogen-13 for an imaging technique called positron emission tomography (PET). PET is used to produce high-quality 3D images of target organs or cells in the body to diagnose disease. Hospitals in Portugal, a country of just 10 million, perform over 50,000 PET procedures per year. Globally, cyclotrons account for 95 per cent of the production of radiopharmaceuticals used in PET.  

These include radiopharmaceuticals whose production had been cumbersome before the involvement of cyclotrons. 

Gallium-68 (Ga-68), for instance, has predominately been produced by a ‘generator’, which can be used for only one year and can create only enough of the radionuclide to cover diagnosis of four to six patients a day. Using cyclotrons, Ga-68 can be produced for up to around 20 patients per day and at a lower cost. At least 10 centres worldwide are now using this approach. The IAEA’s publication, Gallium-68 Cyclotron Production, and a coordinated research project is supporting exchange of international expertise in cyclotron-based production of Ga-68.  

The IAEA is also formulating guidelines to enhance and strengthen the use of zirconium-89 (Zr-89), a PET radioisotope with a relatively long half-life of 3.3 days in comparison to the half-life of flurorine-18 which only lasts one hour and 50 minutes. Zr-89’s half-life provides enough time to be used by medical practitioners to closely observe how molecules in the body behave. It is also applied in clinical trials to detect anti-bodies when a patient is going through cancer therapy.

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