## 2. Techentium-99m Production Routes  
Techentium-99m is easily produced by the decay of the parent molybdenum-99 by eluting compact and transportable \({}^{99}\)Mo/\({}^{99\text{m}}\)Tc generator systems that are almost always available in nuclear medicine departments. The generator system is a simple apparatus composed of an alumina column on which the \({}^{99}\)Mo is absorbed in the chemical form of molybdate [\({}^{99}\)Mo]MoO\({}_{4}\)\({}^{2-}\). The \({}^{99}\)Mo decay into \({}^{99\text{m}}\)Tc leads to the formation of pertechnate [\({}^{99\text{m}}\)Tc]TcO\({}_{4}\)\({}^{-}\), which is less tightly bound to the alumina column because of its single negative charge compared to the double negative charge of molybdate. [\({}^{99\text{m}}\)Tc]NaToO\({}_{4}\) can be easily eluted from the column with a saline solution thanks to the depression caused by an under-vacuum vial appositely inserted in the pertechnate collecting area (Figure 2). The obtained sodium \({}^{99\text{m}}\)Tc-pertechnate is ready for injection or for the preparation of other radiopharmaceuticals [18; 19].  
The worldwide demand for molybdenum-99 is satisfied by nuclear reactors via the \({}^{235}\)U(n,f)\({}^{99}\)Mo fission route on Highly Enriched Uranium targets (HEU, enrichment over 80% in \({}^{235}\)U). Alternatively, molibdenum-99 can be produced by bombarding molybdenum-98 with high-intensity neutrons to generate sufficient amounts of molybdenum-99 [20].  
Nuclear reactors involved in the supply of this isotope are listed in Table 1. In the last decade, they have suffered planned and unplanned shutdowns for maintenance or breakdowns, causing, first in 2009 and then in 2012 and 2013, a shortage in Mo-99 production and therefore in Tc-99m's availability for clinical studies. Recently, significant interruptions in the supply of technetium-99m  
Figure 2. Schematic representation of the \({}^{99}\)Mo/\({}^{99\text{m}}\)Tc generator system.  
occurred in 2016 and 2018, the years when the French OSIRIS and Canadian NRU reactors, respectively, stopped operating.  
In addition to the reactors reported in Table 1, smaller amounts of molybdenum-99 are produced in the RBT-6 and RBT-10 reactors in Russia: irradiating HEU targets have a production capacity of 37,000 GBq/week, and WWR-c has an available production capacity of 12,950 GBq/week. All Mo-99 suppliers except those in Russia produce molybdenum-99 using LEU targets or are in the final stages of converting production from HEU to LEU (Low Enriched Uranium, enrichment below 20% in \({}^{235}\)U) targets [21].  
The supply of molybdenum-99 and technetium-99m is particularly sensitive to reactor shutdowns because, after production, they cannot be stored for future needs due to their short half-lives. Several alternative production routes have been evaluated and some of them have become reliable thanks to the worldwide research efforts of the last 10 years [22; 23; 24; 25]. Alternative strategies for the production of molybdenum-99 include the use of linear accelerators, where a molybdenum-100 source is irradiated with gamma rays, as the \({}^{100}\)Mo(\(\gamma\),\(n\))\({}^{99}\)Mo reaction [26].  
The direct production of \({}^{99m}\)Tc on cyclotrons, involving the proton bombardment of a solid \({}^{100}\)Mo source in the \({}^{100}\)Mo(p,2n)\({}^{99m}\)Tc reaction, is now a reality [23; 27; 28].  
A list of various cyclotron and non-cyclotron production routes is given in Table 2.