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| Fig. 1: An example of a cyclotron at the University of California Lawrence Radiation Laboratory, Berkeley, where many radioisotopes were discovered, including C-14 in 1940. (Source: Wikimedia Commons) |
Radioisotopes, or radioactive isotopes, are unstable atomic nuclei that will emit radiation spontaneously to assume their more stable form. These isotopes offer a variety of critical applications in medicine, both as diagnostic tools and treatment methods. [1] A few current and prospective methods for the production of radioisotopes are detailed below:
Reactor-based preparation of radioisotopes uses the large number of neutrons produced during fission to initiate neutron-based reactions. Thermalized neutrons (low energy), for example, can initiate thermal neutron capture, denoted by (n, γ), in which the atomic nucleus of a target will absorb a low-energy thermal neutron, creating a heavier, unstable isotope. [2] Sometimes, this now unstable nucleus will then decay via β-emission, in a process denoted by (n, γ) → β, which occurs if the (n, γ) reaction produces a short-lived isotope. For example, the radioisotope I-131 (used for thyroid imaging) is produced with (n, γ) → β. Te-130 first captures a thermal neutron, producing Te-131, which then β-decays into I-131. [3] Higher energy neutrons can also be used to produce radioisotopes, inducing reactions in which a charged particle is ejected; in (n, p), for example, neutron absorption induces proton emission, and in (n, α) an alpha particle is emitted. An alternative method for producing I-131 is to take advantage of the fission process itself. The fission of U-235 via thermal neutrons produces a wide range of fission products, including I-131, which can be obtained by separating it out from the uranium fuel cells. [4]
Reactor-based preparation carries a few primary drawbacks. Firstly, the fission process itself produces large quantities of radioactive waste, which remains unclear how to handle. This is problematic no matter which reaction is implemented to produce radioisotopes. Moreover, in the (n, γ) reaction, the product will be an isotope of the target element (ie. Mo-98 absorbs a neutron to become Mo-99), so they cannot be chemically separated. This means that the specific activity obtained, which is a measure of the concentration of radioactivity in a sample, with dimensions of radiation per mass (ie. Ci/g or Bq/kg), will be limited by the neutron flux in the reactor. Low neutron flux means less product will be created and more target remains, thus giving a lower specific activity. [4] Note that high specific activity is desired for medical applications, as it allows small amounts of the desired radioisotope to be administered with minimal toxicity to the patient. (Thermal neutron capture with beta decay and charged particle reactions, on the other hand, produce different elements than the target element, so these can be chemically separated). The fission product method is also challenging because a wide range of elements are produced through fission, and some are isotopes of the desired target species. For example, in addition to producing I-131 during fission, stable I-127 and I-129 are also created, so the specific activity is reduced. In particular, I-131 is contaminated with fission yields of 0.157% for I-127 and 0.54% for I-129. [5]
In contrast to fission reactors, which use neutrons to induce reactions in the target element, accelerators bombard the target with charged particles (generally protons, but sometimes deuterons or helium nuclei are used as well). [6] There are two main types of accelerators: linear accelerators and cyclotrons. Both take advantage of the fact that the energy of a charged particle changes when an electric field is applied to it. Ions in the former are accelerated linearly, while in the latter ions are produced at the center of the machine and accelerated outwards. Fig. 1 shows one such cyclotron in Berkeley, California, where radioisotope carbon-14 was discovered in 1940.
Accelerators can induce several types of reactions. In the (p, n) reaction, a target nucleus is bombarded with a proton, in turn emitting some number of neutrons. The atomic number of the product is thus increased by one in the process. In the (p, α) reaction, absorption of a proton causes an alpha particle to be emitted. In both reactions, evidently, chemical separation is possible, since the product is a different element from the target. Thus, charged particle reactions in accelerators are able to achieve high specific activities. [6]
Accelerators offer a few other advantages over fission reactors. First and foremost, much less radioactive waste is generated in accelerators in comparison to reactors, which generate a plethora of radioactive fission products. Additionally, access to fission reactors is very limited compared to the number of cyclotrons available to the scientific community. Finally, radioisotopes produced in accelerators tend to have more favorable decay characteristics, such as short half-lives, a feature which will be described in more detail below. [6]
The ideal radioisotope has a high specific activity, which is necessary to be able to distribute large amounts of a radioisotope while minimizing the radiation dose to the patient; in diagnostic procedures, for example, large amounts are needed to achieve high counting rates, which enables more accurate and less time-consuming procedures. [7] Unfortunately, high specific activity is also correlated with short half-life, which presents a practicality issue. Radionuclide generators address this challenge by allowing short-lived product radioisotopes to be extracted immediately and continuously from their longer-lived parents. One such system is the Mo-99/Tc-99m generator, which enables the on-site extraction of Tc-99m (with a short half-life of 6 hours) from its parent nuclide, Mo-99 (with a longer half-life of 66 hours). In this system, Tc-99m can be continuously generated from the decay of Mo-99 and used on-site for routine diagnostic imaging. [8]
It is worth mentioning briefly a proposal for extracting radioisotopes from nuclear waste. Specifically, one work suggests a chemical procedure to separate long-lived radioisotopes from short-lived ones. Many medically relevant isotopes are present in radioactive waste from fission reactors, including I-125 (prostate cancer treatment), Y-90 (liver cancer treatment), and Tc-99 (diagnostic imaging). [9] Technically, mining radioisotopes from nuclear waste is conceivable, but unfortunately it is also economically and practically limited. Specifically, medical applications require extreme chemical purity, and the process of achieving appropriate levels of purification for medical use would be extremely costly. As a result, although waste-derived isotopes are of research interest, established production methods like reactors and accelerators remain much more economically practical.
© Maya Benyas. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
[1] E. W. Phelan, "Radioisotopes in Medicine," Oak Ridge National Laboratory, August 1967.
[2] W. Xu, J. Li, and L. Shi, "Study on Producing Radioisotopes Based on Fission or Radiative Capture Method in a High Flux Reactor," Nucl. Eng. Technol. 56, 3585 (2024).
[3] A. F. Rupp and F. T. Binford, "Production of Radioisotopes," J. Appl. Phys. 24, 1069 (1953).
[4] "Manual For Reactor Produced Radioisotopes," International Atomic Energy Agency, IAEA-TECDOC-1340, January 2003.
[5] V. R. Preedy, G. N. Burrow, and R. R. Watson, Comprehensive Handbook of Iodine (Academic Press, 2009).
[6] E. Cazzola, C. Favaretto, and G. Gorgoni, "Cyclotron Radioisotope Production: Developments and Challenges in the New Era," in Automated Technologies for the Development and Production of Radiopharmaceuticals, ed. by R. M. Van Dam, Y. Kuge, and G. Pascali (Springer, 2025), p. 3.
[7] E. Lebowitz and P. Richards, "Radionuclide Generator Systems," Semin. Nucl. Med. 4, 257 (1974).
[8] S. Chattopadhyay and M. K. Das, "A Novel Technique For the Effective Concentration of 99mTc From a Large Alumina Column Loaded With Low Specific-Activity (n,γ)-Produced 99Mo," Appl. Radiat. Isot. 66, 1295 (2008).
[9] M. L. Terranova and O. A. P. Tavares, "Trends and Perspectives on Nuclear Waste Management: Recovering, Recycling, and Reusing," J. Nucl. Eng. 5, 299 (2024).
