The historical motivation of the large particle accelerators created in the 20th century was initially focused on the field of basic science, but today their applications have spread to improve the daily lives of mankind. These include aspects as varied as the preservation of food, the purification of water, the manufacture of semiconductors, the creation of biomolecules, the construction of new polymeric materials and, above all, medicine and pharmacology.
Nuclear medicine uses atoms of the same element whose nuclei have a different number of neutrons, which are called isotopes or radioisotopes if they also emit some particle.
These radioisotopes have been manufactured in recent decades for various medical uses such as therapy and computerized imaging. The most widespread technique for computerized imaging using radioisotopes is called SPECT (Single Photon Emission Computer Tomography), through the isotope Technetium-99m (99mTc), which emits photons (gamma rays).
This drug basically consists of a micro-lantern that illuminates the human body. The SPECT scanner, through a camera sensitive to these photons, rotates around the patient and captures complete images that a computer classifies into sections. The production of 99mTc has been carried out for decades in nuclear reactors using decay of Molybdenum-99 and in the last decade also by means of proton accelerators that IAEA (International Atomic Energy Agency) propone utilizar.
One of the most useful medical diagnostic visualization techniques in practice is called PET (Positron Emission Tomography). Although PET is still used less than the previous SPECT –partly due to its relative high cost– it has improved and its use is much broader in medicine, given that the image obtained generates much better resolution. For this reason, his interest has expanded in recent years to different specializations of nuclear medicine.
The imaging of new PET using various radiopharmaceuticals is, therefore, a field of research of extraordinary importance for current biomedicine.
PET radiopharmaceuticals
Various short-lived positron emitters are of primary importance for medical diagnostics by means of PET. Some of the radioisotopes that can be manufactured using low energy accelerators are Fluorine 18, Oxygen 15, Nitrogen 13 and Carbon 11 (18F, 15O, 13N and 11C, respectively).
Since positrons are the antimatter of electrons, these radiopharmaceuticals emit positrons which, colliding with electrons in the patient’s body, generate photons that create an image. This is processed by computer so that medical personnel can see and diagnose.
These drugs behave like nanolinternas that allow high-resolution images to diagnose multiple pathologies.
A logistical challenge
Fluorine 18 is one of the most used isotopes in many hospitals. It can be manufactured externally, since it has a short but long enough half-life (approximately 110 minutes), so that it can be sent to the medical center from outside.
Even so, external shipment requires the manufacture of many more doses of high radioactive activity, since some of it decays and deactivates during the hours of transport. Globally, therefore, the current external manufacturing of the radiopharmaceutical requires excesses in economic, energy, radioactive and speed terms. The efficiency of these issues can be improved by local manufacturing of customized pharmaceutical doses in the hospital itself.
Oxygen, Nitrogen and Carbon are very important elements, since they constitute the cells of the human body and can be used to label a wide variety of useful pharmaceutical compounds.
However, the short half-life of its isotopes (between two and twenty minutes) requires local manufacturing within the hospital itself. This implies the impossibility of its medical use unless it is manufactured immediately and without the need for transport.
There is a lot of interest in these other radiopharmaceuticals for PET, which are still rarely used in medicine. In particular, the great interest in 11C, which can replace ordinary 12C in any molecule in the human body, is very notable.
In this case of the Carbon 11 radioisotope, we can imagine that the nano-lantern that illuminates the PET images spends its battery in a few minutes and following working it disappears without needing to be removed.
The local manufacture of all kinds of PET radiopharmaceuticals is, therefore, an important applicability for biomedicine. The local and tailor-made manufacture of these promising isotopes using compact accelerators would allow their real medical use.
Accelerators for radiopharmaceutical production
The most common way of manufacturing radiopharmaceuticals are nuclear reactors or particle accelerators. The most common way today is the use of cyclotrons, which have been used for several decades.
These devices are heavy and bulky, often accelerating protons to energies of tens of MeV (Mega Electron Volts) in medical applications. Its cost of manufacture and operation, maintenance and energy expenditure is high and prevents hospitals from generalizing its use.
Linear accelerators (LINear ACcelerator, LINAC), in particular a new compact generation, have several advantages over traditional cyclotrons.
In the first place, Linacs have lower beam losses compared to cyclotrons, since the latter, due to their circular nature, are subjected at all times to the centripetal Lorentz force that radiates photons tangentially and the beam loses energy.
Secondly, the new generation of Linacs are much more compact, economical, lighter, and with low requirements, both in terms of energy expenditure and radioactive protection.
Due to these numerous advantages, this type of accelerator becomes an excellent alternative for producing radiopharmaceuticals in the hospital itself at low proton energy.
Linac 7 Project
Linac 7 is a project consisting of a new generation proton linear accelerator completely conceived, designed and built in the Particle Beam Laboratory (IZPILab-Beam Laboratory) of the University of the Basque Country UPV/EHU, and many of whose components are currently in operation.
One of the most important health applications conceived within this project is the production of drugs of various kinds, locally around large clinical centers. The dimensions and characteristics of the accelerator can serve a hospital in an internal laboratory or even allow it to be shipped on a small truck to share an on-demand radiopharmaceutical manufacturing schedule in multiple medical facilities that request it.
There is a lot of interest in Europe for the use of different options of particle accelerators for the manufacture of medical radioisotopes. In particular, the European Commission promotes the ARIES Consortium (Accelerator Research and Innovation for European Science and Society), whose report, published on June 22, 2020, describes the current state of the manufacture of medical radioisotopes with accelerators and expresses very specifically the scientific, medical and industrial interest in the development of new Linacs for PET.
