Challenges and future options for the production of lutetium-177

Abstract

The use of the medical isotope lutetium-177 is increasing, but there are concerns that its worldwide availability may not be sufficient in the long term. This warrants an evaluation of its use and production. Nuclear medicine involves the use of a spectrum of radioactive isotopes for diagnostic and therapeutic purposes, for example to identify cardiovascular and inflammatory diseases or to treat various types of cancer. The applied techniques require various isotopes with different physical properties. Isotopes for diagnostic purposes (gamma or positron emitters) typically decay with half-lives in the range of minutes to hours, while therapeutic isotopes (electron or alpha emitters) generally have half-lives of days to weeks. Because of this continuous loss by decay, in combination with the need to provide timely medical procedures for all patients in need, nuclear medicine requires uninterrupted and sufficient supply of relevant medical isotopes. The applied medical isotopes have different requirements for production and distribution. For example, isotopes with longer half-lives like molybdenum-99 (Mo) and lutetium177 (Lu) are typically produced by fission or activation in a nuclear reactor, and are then distributed to medical centres worldwide. Shorter lived isotopes cannot be transported over longer distances and need to be produced locally or regionally. Typical examples are technetium-99 m that is derived using a mother-daughter generator, and fluor-18 that is produced using a cyclotron. Continuous availability of all these production techniques at optimal locations is essential, in order to warrant adequate supply of every required isotopes throughout the world. However, there is no central planning for the future of worldwide isotope production. In 2008–2010, the world started to notice this because the situation was dire: two of the main isotope-producing reactors at the time, the NRU in Canada and the HFR in the Netherlands, were both not operational unexpectedly, leading to a world-wide shortage of several medical isotopes. This caused important delays in diagnostic imaging and in treatment of cancer, and many centres struggled to find workable alternative strategies to provide adequate medical care for their patients [1]. This very challenging situation gave rise to international discussions, and efforts to improve the reliability and economic sustainability of the current production infrastructure world-wide. The OECD/NEA started the High Level Group Medical RadioIsotopes (HLG-MR), and the EU started the European Observatory on the supply of medical radioisotopes. The situation also sparked new discussions about the future of reactor-based isotope production, and investments in nuclear production reactors are currently subject of political debate. In addition, several new alternative production methods have been proposed. Upon weighing the options for future production, it will be important to consider all relevant medical applications and their associated isotopes. However, recent discussions and proposed alternative techniques to generate isotopes are almost exclusively focussed at Mo [2]. Since production of different isotopes poses different technological challenges, this may lead to future situations where not all required isotopes can be produced with sufficient quantity, quality, reliability or geographic spread. We identify Lu as an important example of a medical isotope that may be at risk for future shortages. The increasing demand for Lu is explained by its application in several current and new radionuclide therapies, most notably radiolabelled somatostatin analogs for neuroendocrine tumours and PSMA-ligands prostate cancer. In combination This article is part of the Topical Collection on Editorial.