New production method promises to end global shortages of medical radioisotopes
A diagram of the 99month/99mTc production system based on an electron linear accelerator and based on activated carbon 99mTc generator.
©2022 University of Tokyo
A commonly used radioisotope, technetium-99m, used in medical diagnostics regularly suffers shortages due to its production in aging nuclear reactors that often shut down for repair. But an alternative technique for producing the isotope, developed by a group of researchers at the University of Tokyo and taking advantage of equipment commonly found in hospitals, promises to put an end to those supply chain frustrations.
A paper describing the method and its effectiveness in mouse test subjects was recently published in the journal Nuclear Medicine Biology.
Technetium-99m (99mTc) is one of the most commonly used medical radioisotopes in the world, thanks to the unique properties of its radioactivity. It emits moderate energy gamma rays that are easily detected by medical equipment. 99mTc also has a moderately short half-life which allows its gamma emissions to be used as a tracer in medical diagnostic procedures while keeping patient radiation exposure very low.
This radioisotope is produced from molybdenum-99 (99Mo), which is produced by the fission of uranium 235 in nuclear reactors. Most of the reactors producing the vast majority of the world’s supply of 99mTCs are quite old now and are often closed for long periods for repairs, threatening the availability of this vital medical product. A global shortage of 99mTc happened in 2010 when two of the 99Mo production reactors were offline at the same time, prompting a search for alternative methods of 99month/99mCT production.
One of the most promising alternatives is the use of a linear particle accelerator (or “linac”), instead of nuclear reactors. A linac accelerates charged subatomic particles to a very high speed along a straight line, as opposed to accelerating around a loop (thus “linear”). the 99Mo is produced by irradiating molybdenum trioxide with photons from the linac electron beams, and the 99mTc extracted from decomposition 99Mo by a technetium-99m generator, sometimes referred to as a “cow moly” by its operators.
What makes this alternative to reactors so attractive is that the relatively compact linacs are already widely used in hospitals for radiotherapy of cancer patients.
A challenge this option has faced, however, is that for the 99mTc to be usable as a medical tracer, the element must have a high radioactive concentration (RAC — the amount of radioactivity per volume), and the 99The Mo precursor produced with linacs has a much lower level of “specific activity” (emissions per mass of molybdenum) than that produced as a result of nuclear fission. the 99Mo can lead to 99mTc having a BCR that is too low if the 99mThe Tc is extracted using aluminum oxide (alumina) as a filter in the molybdenum machine.
To solve this problem, researchers at the University of Tokyo replaced alumina with activated carbon (sometimes called activated carbon, or simply AC), a type of carbon that has been specially treated to have many tiny pores. These pores deeply improve the surface of the substance, thus also improving the places where atoms can adhere (and therefore be extracted). For this reason, activated carbon is widely used in air filters, wastewater treatment, decaffeination, and gold purification. This attribute also makes it ideal for focusing the 99mTc and can be used even with 99Mo with low specific activity.
“We had previously demonstrated the practicality of this combined linac-AC method to produce medically usable products. 99mTc, but had not yet done preclinical or clinical trials to see if in the body, this alternatively produced radioisotope is as effective as the conventionally produced one,” said Jaewoong Jang, an assistant professor at the university. and lead author of the study. “We had a great concept, but we weren’t sure if it would be what we call ‘bioequivalent’ – essentially, would work the same way in patients.”
So they injected a group of mice with linac-AC derived 99mTc as pertechnetate (the most basic compound of technetium used in radiopharmaceuticals) and another group of mice with the conventionally produced compound 99mTc. The mice were then dissected to assess the spread (“biodistribution”) of the radioisotope in different organs.
Both types of 99mTc radiopharmaceuticals showed similar distribution in all organs and tissues examined, and no adverse effects in mice were observed, suggesting the clinical applicability of linac-AC derivatives 99mTc radiopharmaceuticals.
The study was preliminary, with evaluation not taking place until some time after injection of the radioisotope. The researchers now want to perform additional biodistribution studies at different times to fully confirm the bioequivalence of the two 99mTc methods.