# Highly Enriched Uranium-Free Medical Radioisotope Production Methods: An Integrative Review
## 1 Introduction
This process produces over forty distinct radioisotopes [24], including the \({}^{99}\)Mo (half-life of 66 h), which later decays to \({}^{99\text{m}}\)Tc in a \({}^{99}\)Mo/\({}^{99\text{m}}\)Tc generator. Due to the molybdenum's large half-life, this generator can be transported all over the world to support the worldwide medical demand of \({}^{99\text{m}}\)Tc. Despite the significant advantages of the radioisotope production scale, multiple substantial concerns are associated with the fission of HEU in research reactors. The first (and most dangerous) one is the generation of large amounts of environmentally hazardous radioactive waste, which can take from decades to hundreds of years to decay. Dealing with radioactive waste often requires relocating and storing it in a deep-underground repository [25], which leads to storage space/safety problems since the waste can be active for hundreds of years. Another issue caused by having most of the radioisotope production centralized in research reactors is the consequent need of transporting highly radioactive material over long distances [26]. Although this activity has been safely and efficiently conducted for several decades [27], there are issues associated with it, such as the higher production costs and logistics complexities, which are even more critical for developing countries [28]. Finally, as mentioned by ([PERSON], [PERSON] 2013) [29], the shutdown of two research reactors in 2009, the Chalk River reactor (in Canada) and the Petten high flux nuclear reactor (in the Netherlands), made it clear that the world's radioisotope supply chain was fragile, as it greatly relied on a few research reactors built in the 1950s and 1960s. In those times, these two reactors were responsible for producing most of the world's supply of \({}^{99\text{m}}\)T; thus, the shutdowns created a shortage of this radioisotope. This crisis motivated the research into \({}^{99}\)Mo production in cyclotrons via proton irradiation, and in linear accelerators via the bremsstrahlung \(\gamma\)-ray reaction route \({}^{100}\)Mo(\(\gamma\),n)\({}^{99}\)Mo [29]. In addition to the aforementioned issues associated with using research reactors, international nuclear non-proliferation policies emphasize the need of eliminating the use of HEU for medical radioisotope production [30]. Hence, developing alternatives to the HEU-based production methods, i.e., HEU-free production routes through different acceleration technologies and/or physical processes, is a crucial step toward finding a greener solution to meet the ever-growing demand for medical radioisotopes. In order to contribute to this relevant topic, this integrative review [31] aims to identify and synthesize the recently reported HEU-free medical-radioisotope production methods, as well as the medical radioisotopes produced by using such methods. This review is organized as follows. Section 2 presents an overview of the method adopted for the literature review and describes the process used to analyze the results. In Section 3, the results obtained are presented and discussed. Finally, in Section 4, the conclusions and future directions are presented.