The radionuclides used to make radiopharmaceuticals are produced artificially, mainly in a nuclear reactor or in a cyclotron. The type of radionuclides produced in a cyclotron or in a reactor depends on the type of energy of the bombarding particles and the target material.

Production techniques involve bombarding the nuclei of a target with high-energy particles, transforming the stable nuclides into radioactive nuclides (radionuclides).

This nuclear transmutation process takes place in two stages. In the first stage, the bombarding particles penetrate and are captured by the nuclides of the target, transferring their kinetic and binding energy to it – generating an intermediate energy state in the target’s new nuclides.

In the second stage, one or more nucleons may overcome the nuclear binding energy and escape. The escaping particles may carry all their energy with them or only the amount required to escape. The energy that does not escape with these particles is released in the form of radiation from the new nuclide. The types of particles that can escape vary, although they consist basically of: protons (1H+), deuterons (2H+), neutrons (n) and α particles (4He2+).

The radionuclides produced by the cyclotron are characterized by a presence of fewer neutrons, and their nuclear stability is obtained through electron capture or positron emission.

A cyclotron is a charged particle (cation or anion) accelerator that transfers high energy to these particles, accelerating them in circular orbits by means of alternating electromagnetic fields until they collide with a target, with the consequent nuclear reaction and the production of positron-emitting radionuclides. The cyclotron was developed by E.O. Lawrence and M.S. Livingston in 1934 with the purpose of accelerating particles such as protons or deuterons to achieve high levels of kinetic energy.

All cyclotrons are comprised of two electrodes in the form of semi-circular chambers (D) in which a vacuum is produced, and they are configured with the adjacent perimeter diameters in a uniform magnetic field. The Ds are coupled to a high-freque ncy electrical system that alternates about 107 times a second while the cyclotron is operating.

In each D, the ions are forced into a circular trajectory by means of an alternating magnetic field. When the ions complete a semi-circumference in the semi-period, the electrical field inverts polarity, causing acceleration of the ions in the electrical fields between the Ds, while also increasing the radius of their circular trajectory. This increase in acceleration involves an increase in kinetic energy.

This process is repeated continuously, in semi-circular orbits that move in resonance with the oscillating field. In this way they gain energy continuously, describing a spiral trajectory until the periphery of the Ds is reached with the energy needed to escape from them and collide with the target, where the nuclear reactions will take place.

In these nuclear reactions, the impacting particle can exit the nucleus after the interaction, leaving part of its energy in the nucleus, or it may be completely absorbed by the latter. In either case, a nucleus in an excited state is generated, and the excitation energy is released through the emission of nucleons (i.e., protons and neutrons). The emission of gamma radiation then occurs. Depending on the energy transmitted by the impacting particle, a random number of nucleons are emitted from the irradiated target, resulting in the formation of different nuclides. When the energy of the irradiating particle increases, more nucleons are generated and a greater variety of radionuclides are therefore produced. The radionuclides produced in a cyclotron are generally neutron-deficient and therefore decay with the emission of β+ particles or through electron capture.

Radionuclides produced by the cyclotron and which are of interest in nuclear medicine comprise:

  • Fluor-18: 18F
  • Carbon-11: 11C
  • Nitrogen-13: 13N
  • Oxygen-15: 15O
  • Gallium-68: 68Ga
  • Scandium-44: 44Sc
  • Zirconium-89: 89Zr
  • Iodine-124: 124I

The production of radionuclides of interest in nuclear medicine generated in nuclear reactors is based on two types of nuclear reactions involving an interaction with neutrons: neutron capture and the fission of heavy elements.

In neutron capture, the target nucleus captures a thermal neutron, emitting gamma radiation to produce an isotope of the same element as the target nuclides. Some examples of radionuclides produced by this type of reaction are 131Te, 99Mo, 197Hg, 59Fe, 51Cr, etc.

Fission of heavy elements is characterized by the splitting of a heavy nucleus into two fragments of approximately the same mass, accompanied by the emission of two or three neutrons. Each fission reaction releases a substantial amount of energy that is extracted through heat exchangers to produce electricity in nuclear energy plants. When a fissionable heavy element target is inserted into the core of the reactor, the heavy nuclides absorb thermal neutrons and undergo the so-called fission reaction. Some fissionable heavy elements with an atomic number over 90 are: 235U, 239Pu, 237Np, 233U 232To. On the other hand, many clinically useful radionuclides such as 131I, 99Mo 133Xe and 137Cs are obtained from the fission of 235U.