Cyclotron is an accelerator of charged particles used in the Radiopharmaceuticals Production Center of BraIns to produce nuclear reactions. It is located on the first floor of the building, inside a room with 2-meter thick walls, ceiling and door, the so-called bunker. Equipment operation is entirely remote. The bombardment of atomic nuclei with protons accelerated by the cyclotron allows the production of radioactive isotopes used in PET/CT studies, especially18F.
Components of the Cyclotron
The cyclotron is composed of three major components: a magnet, a pair of semicircular hollow electrodes, the so-called Dees, responsible for accelerating charged particles, and a source of ions that can generate electrically charged particles. The Dees and the ion source are kept in a vacuum tank (lower pressure at 10-6 mbar).
Operating Principle of the Cyclotron
Essentially, after the ionization of hydrogen gas in the ion source, H-ions are injected between the Dees.
The alternation of electrical potential between the Dees, generated by a radio frequency wave, is responsible for the acceleration of ions inside the tank. The magnet generates a field that keeps the particles confined and moving in circular orbits. As the particles gain energy from acceleration, the radius of these orbits increases until they accumulate sufficient kinetic energy to be released at the target. The passage of negatively charged ions through an ultrathin carbon foil (stripper), which extracts their electrons, changes their charge and trajectory. This change removes the ions from the tank and allows them to go inside the nuclei of the 18O atoms to produce the radioactive isotope 18F.
What is the radiopharmaceutical [18F] FDG and how is it produced?
The radiopharmaceutical [18F]FDG or Fludeoxyglucose (18F) is currently the most widely used radiotracer for PET/CT imaging. This molecule is analogous to the glucose molecule and is used to map glucose metabolism in the organism. [18F]FDG was the first radiopharmaceutical to be produced in the Radiopharmaceuticals Production Center of BraIns. The drug is administered to patients in the Molecular Imaging Center on the second floor of the building, where the PET/CT (Positron Emission Tomography/Computed Tomography) equipment is located. FDG can detect anatomical and functional changes in the body, since it presents high affinity for areas with increased glucose metabolism, showing the position and the functional activity of fast-growing cancer cells, as well as the emergence of metastases. Tumors can thus be detected much earlier with this method than with the use of other available techniques.
The manufacture of radiopharmaceuticals in our facilities shows our constant pursuit of technological innovation and a diagnostic and therapeutic advancement. A major difference at BraIns is that the cyclotron (particle accelerator – source of radioisotopes) and PET/CT equipment are located in the same facilities, which enables the use of radiopharmaceuticals with ultra-short half-life, such as 11C–PIB (20-minute half-life), a marker of beta-amyloid plaques characteristic of Alzheimer’s disease. Other radiotracers labeled with Carbon 11 will be used in pilot projects and will be available at InsCer in the near future.
… Nuclear Medicine has its origins in the pioneering work of the Hungarian physician George de Hevesy, who, in 1924, used radioactive isotopes of lead as tracers in bone studies. However, it was the discovery of artificial radioactive elements that increased the number of elements for use as tracers. In 1932, the invention of the cyclotron by E. Lawrence made it possible to produce radioactive isotopes of various biological elements. The use of these artificially produced radiotracers continued with Hamilton and Stone, who clinically used radioactive sodium in 1937. In 1938, Hertz, Roberts and Evans used radioactive iodine to study the physiology of the thyroid.
… the kinetic energy gained by ions in the cyclotron is equal to the energy gained by one electron submitted to a potential difference of 16 million volts.
… the first medical cyclotron was installed in 1941 at Washington University, St. Louis, where radioactive isotopes of phosphorus, iron, arsenic and sulfur were produced. With the development of the fission process during World War II, most medically important radioisotopes began to be produced in reactors. After the war, the use of radioactive material in medicine began to spread, establishing a new field called atomic medicine, which later came to be known as nuclear medicine (AIEA 2008; Vallabhajosula et al. 2011).
… the radiopharmaceutical [18F]FDG (Fludeoxyglucose 18F)) was first produced for use in humans in 1976 at the Brookhaven National Laboratory (NY, USA) and the first image was made at the Hospital of the University of Pennsylvania (USA).
Sources: João Alfredo Borges (medical physicist), Louise Mross Hartmann (coordinator of the Radiopharmaceuticals Production Center), and Cristina Maria Moriguchi Jeckel (professor at PUCRS School of Pharmacy and researcher at InsCer).