# Highly Enriched Uranium-Free Medical Radioisotope Production Methods: An Integrative Review
## 4 Conclusions and Future Directions  
An integrative review of alternative methods for radioisotope production was carried out. Papers containing experimental production results, published from 2010 to 2021,were considered. A total of 48 papers were selected and analyzed. Among these works, cyclotrons were the most adopted particle accelerator technologies for radioisotope production, followed by HEU-free research reactors. Combined, these two methods were adopted in nearly 94% of the papers evaluated in this review. Regarding the radioisotopes, the most-cited one was \({}^{44}\)Sc, with seven distinct citations, followed by \({}^{68}\)Ga and \({}^{99\mathrm{m}}\)Tc with four citations, and \({}^{66}\)Ga, \({}^{99}\)Mo, and \({}^{89}\)Zr with three citations each. All of these radioisotopes are applied in PET (\({}^{44}\)Sc, \({}^{68}\)Ga, \({}^{66}\)Ga, \({}^{89}\)Zr), or SPECT (\({}^{99}\)Mo, \({}^{99\mathrm{m}}\)Tc) diagnoses. It is clear that new compact, environmentally safe, and cost-effective technologies for producing radioisotopes are needed, and that there is interest from the scientific community in developing new, HEU-free production routes that mitigate the generation of radioactive waste. Moreover, new, decentralized production methods could minimize possible future problems similar to the shortage crisis of \({}^{99}\)Mo/\({}^{99\mathrm{m}}\)Tc generators in 2009. As shown in this review, HEU-free medical-radioisotope production methods have been adopted and reported in the last decade. However, more research in this area is crucial for attaining greener and high-yield radioisotope production methods, capable of competing with the current uranium-based standard production techniques. A possible alternative would be producing radioisotopes via reaction routes triggered by bremsstrahlung \(\gamma\)-rays, obtained, for example, from the deceleration of high-energy electron beams. Depending on the target material, it is possible to estimate the energy range required for the photons to trigger photonuclear reactions capable of producing the radioisotope of interest. Moreover, as in this process, the radioisotope of interest is a product of the reaction, rather than a byproduct, as in the case of nuclear fission, the adoption of this process would mitigate the radioactive waste. Despite being reported in the literature as a possible scheme for producing radioisotopes [104,105], such as, for example, the \({}^{99}\)Mo (which decays to \({}^{99\mathrm{m}}\)Tc) [105,106], no experimental works were found among the papers selected for this review according to the aforementioned criteria. The high-energy electron beams required to generate bremsstrahlung photons capable of producing radioisotopes via photonuclear reactions might be soon attainable by using laser wakefield accelerators (LWFAs) [107,108]. In this scheme, under the proper conditions, an intense laser pulse propagating in plasma drives a high-amplitude wakefield on its trail, which can be used as a compact accelerating structure for the plasma electrons (self-injection), or for an externally injected electron beam. LWFAs are capable of producing eight GeV electron beams at the exit of a 20 cm-long plasma capillary [109]. Moreover, stable long-term kHz operations of LWFAs have recently been reported [110]. In addition to the low amount of radioactive waste produced via bremsstrahlung \(\gamma\)-rays reaction routes, the compactness of this technology could allow for local radioisotope production, mitigating the aforementioned transportation problems associated with other technologies that require centralized production. Despite the LWFA being a promising technology [111], recent studies [106,112,113] indicate that, even if high-energy, high-repetition-rate laser systems are adopted, due to the low yield provided by the photon activation process, very long irradiation times would still be required to produce a given radioisotope in quantities that could supply typical daily doses for medical applications.