New strategies for a sustainable (99m)Tc supply to meet increasing medical demands: Promising solutions for current problems

The continuing rapid expansion of (99m)Tc diagnostic agents always calls for scaling up (99m)Tc production to cover increasing clinical demand. Nevertheless, (99m)Tc availability depends mainly on the fission-produced (99)Mo supply. This supply is seriously influenced during renewed emergency periods, such as the past (99)Mo production crisis or the current COVID-19 pandemic. Consequently, these interruptions have promoted the need for (99m)Tc production through alternative strategies capable of providing clinical-grade (99m)Tc with high purity. In the light of this context, this review illustrates diverse production routes that either have commercially been used or new strategies that offer potential solutions to promote a rapid production growth of (99m)Tc. These techniques have been selected, highlighted, and evaluated to imply their impact on developing (99m)Tc production. Furthermore, their advantages and limitations, current situation, and long-term perspective were also discussed. It appears that, on the one hand, careful attention needs to be devoted to enhancing the (99)Mo economy. It can be achieved by utilizing (98)Mo neutron activation in commercial nuclear power reactors and using accelerator-based (99)Mo production, especially the photonuclear transmutation strategy. On the other hand, more research efforts should be devoted to widening the utility of (99)Mo/(99m)Tc generators, which incorporate nanomaterial-based sorbents and promote their development, validation, and full automization in the near future. These strategies are expected to play a vital role in providing sufficient clinical-grade (99m)Tc, resulting in a reasonable cost per patient dose.