In this work, ^177mLu has been produced by irradiation of natural Lu₂O₃ targets at the BR2 reactor (Mol, Belgium) and the obtained data together with literature values have been used to theoretically investigate the production of ^177mLu at different neutron fluxes, irradiation times and enrichment of ¹⁷⁶Lu. The irradiation time (t_max) needed to reach the maximum ^177mLu production has been found to change from 42, 12, 4 days with the increase in the thermal neutron flux from 2*10¹⁴, 8*10¹⁴, 2.5*10¹⁵ n cm⁻² s⁻¹, respectively while keeping the maximum ^177mLu activity unaffected. The results of our calculations suggest that 0.11 TBq ^177mLu with a specific activity of 0.3 TBq g⁻¹ Lu can be produced in a short irradiation time of 4 days using 1g of 84.44% ¹⁷⁶Lu enriched Lu₂O₃ and a thermal neutron flux of 2.5*10¹⁵ n cm⁻² s⁻¹.

A solid phase extraction based ^177mLu-¹⁷⁷Lu separation method has been investigated for its feasibility to be used in the radionuclide generator. The use of 2,2′,2”-(10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid, (DOTAGA-anhydride) allowed grafting of DOTA (1,4,7,10-tetraazacyclododecane N,N′,N″,N‴-tetraacetic acid) complex on the surface of commercially available amino propyl silica. The grafting of DOTA has been confirmed by several characterization techniques. The thermogravimetric analysis reveals that the 0.33 mmol DOTA groups have been grafted per gram of silica. However, during the Lu ion complexation, a 10 times lower Lu adsorption capacity of 0.03 mmol g⁻¹ could be achieved under the studied reaction conditions. The results indicate that the grafting of DOTA on solid affects the Lu coordination and also influences the kinetics of Lu-DOTA complexation. The weak coordination resulted in high ^177mLu leakage, while the unreacted DOTA groups interfer with the ¹⁷⁷Lu release. This is evident from the 0.3% ^177mLu leakage combined with a¹⁷⁷Lu extraction efficiency of 25%. Overall, the results show a^177mLu-¹⁷⁷Lu separation with a maximum ¹⁷⁷Lu/^177mLu activity ratio of 25. But this is still far away from clinically acceptable activity ratio of 10,000 for which future work is recommended.

In order to determine the potential of ^177mLu/¹⁷⁷Lu radionuclide generator in ¹⁷⁷Lu production it is important to establish the technical needs that can lead to a clinically acceptable ¹⁷⁷Lu product quality. In this work, a model that includes all the processes and the parameters affecting the performance of the ^177mLu/¹⁷⁷Lu radionuclide generator has been developed. The model has been based on the use of a ligand to complex ^177mLu ions, followed by the separation of the freed ¹⁷⁷Lu ions. The dissociation kinetics of the Lu-ligand complex has been found to be the most crucial aspect governing the specific activity and ^177mLu content of the produced ¹⁷⁷Lu. The dissociation rate constants lower than 1*10^-11 s^-1 would be required to lead to onsite ¹⁷⁷Lu production with specific activity close to theoretical maximum of 4.1 TBq ¹⁷⁷Lu/mg Lu and with ^177mLu content of less than 0.01%. Lastly, the calculations suggest that more than one patient dose per week can be supplied for a period of up to 7 months on starting with the ^177mLu produced using 3 g Lu₂O₃ target with 60% ¹⁷⁶Lu enrichment. The requirements of the starting ^177mLu activity production needs to be adapted depending on the required patient doses, and the technical specifications of the involved ^177mLu-¹⁷⁷Lu separation process.