Radioiodine Production

Radioiodine is defined as a radioactive isotope of the chemical element iodine. Although there are at least 37 different iodine radioisotopes, only four of them are used as tracers or therapeutic agents in medicine; these are I-123, I-124, I-125, and I-131, with the latter being the most common in clinical practice. Essentially all industrial production of radioiodine isotopes involves those four aforementioned radionuclides.

iodineImage Credit: Sadovnikova Olga/

History of radioiodine production and usage

The first radioiodine was produced by Enrico Fermi in 1934. It was Iodine-128, which prompted additional experiments in France and the United States. Karl Compton and the thyroid group from the Massachusetts Institute of Technology and Massachusetts General Hospital, respectively, were responsible for research endeavors that eventually led to the production of short-lived Iodine-128 in small amounts.

By 1941, Iodine-130 and Iodine-131 were the first radioiodine isotopes used for the treatment of thyrotoxicosis, and in 1943 their usage extended to thyroid cancer. When fission-derived radioiodine became freely available in 1946 as a consequence of the Manhattan project in a secret town named Oak Ridge, hundreds of patients underwent treatment within a few years.

Reactor produced radioiodine

Iodine-131, the most commonly used radioiodine isotope in the treatment of thyroid diseases, is a reactor-produced radionuclide which is commercially available in large quantities. Two main routes for its production are fission of the Uranium-235 isotope and so-called (n, γ) reaction.

As the chain yield of Iodine-131 is considerably high and the radioiodine isotopes with mass higher than 131 are short-lived, this radioisotope is easily obtained in pure form. Irradiated Uranium-235 is first stored for 24 hours in order to allow decay of short-lived products and treated with sodium hydroxide.

After filtration (where uranium and certain fission products are removed), the filtrate is acidified with nitric acid. On heating, radioiodine is distilled over and collected in the trap, while the rest of the reaction mixture is treated further for separation of Molybdenum-99 and other fission products.

On the other hand, the (n, γ) reaction on Technetium-130 leads to the formation of Technetium-131m and Technetium-131g. The target material for irradiation is either TeO2 or Te-metal, depending on whether a wet chemical separation or a dry distillation method is used.

Iodine-131 is commercially available in dilute sodium hydroxide solution with high radiochemical purity. In certain solutions a specific reducing agent needs to be added to preserve the isotope in the form of iodide; however, its use may interfere when employing Iodine-131 for labelling organic compounds.

Iodine-125 is also a reactor-produced radionuclide that also follows the (n, γ) reaction on Xenon-124. Iodine-125 is commercially available in dilute sodium hydroxide solution with high chemical and radiochemical purity. Its radioactive concentration lies at 4 to 11 GBq/ml.

Cyclotron produced radioiodine

Iodine-123 represents widely used cyclotron-produced radioisotope for single-photon emission computed tomography (SPECT). Nuclear reaction which yields Iodine-123 directly via proton bombardment of tellurium targets in a cyclotron with subsequent separation of this radioiodine from the irradiated target represents the process that is most commonly utilized.

Nuclear reactions used for Iodine-123 production can be indirect as well, where precursor Xenon-123 (with a half-life of 2.1 hours) is used. In this class or reaction, gaseous and chemically inert Xenon-123 is separated from the irradiated target and then allowed to decay to Iodine-123. This route results in higher product purity when compared to the direct route.

Finally, Iodine-124 (which can be used both as a diagnostic and a therapeutic radionuclide) is also produced at a cyclotron. Thus far no commercial supplier has undertaken the responsibility to produce this radioiodine in large quantities, but the demand for this radioisotope is increasing (namely for research purposes).


Further Reading

Last Updated: May 7, 2021

Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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  1. Nic Mastascusa PharmD, RPh, BCNP Nic Mastascusa PharmD, RPh, BCNP United States says:

    The neutron activation reaction (n,gamma) to produce iodine-131 is not technetium-130, it is tellurium-130.  The symbol for Technetium is Tc, Tellurium is Te.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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