Production routes of the alpha emitting ¹⁴⁹Tb for medical application

Summary

The partial alpha emitting lanthanide isotope ¹⁴⁹Tb seems to have a great potential in systemic radioimmuno therapy (RIT), especially when single cells in transit or circulation are targeted. The isotope ¹⁴⁹Tb has a half life of 4.118 h and decays by alpha emission (3.97 MeV, 17%) EC-process (76%) and β⁺-emission (7%). In this paper, we analyze the possible production routes: light- and heavy ion induced nuclear reactions and p-induced spallation.

The excitation functions for light- and heavy ion induced reactions have been calculated using the ALICE91 code. The direct nuclear reaction ¹⁵²Gd (p, 4n) ¹⁴⁹Tb was found to be the most promising production path. Alternatively, the indirect reaction ¹⁴²Nd (¹²C, 5n) ¹⁴⁹Dy → ¹⁴⁹Tb seems to be much more suitable compared to the reaction on the mono-isotopic target element ¹⁴¹Pr ¹²C, 4n) ¹⁴⁹Tb. In this case, both, the production yield of ¹⁴⁹Tb and the radionuclidic purity are considerably lower, compared to the (p, 4n)-reaction. In preliminary experiments we produced ¹⁴⁹Tb via the indirect reaction Nd (¹²C, 5n) ¹⁴⁹Dy → ¹⁴⁹Tb (108 MeV ¹²C⁺⁶ ions and 1 particle-µA) at the U-200 heavy ion cyclotron at the FLNR of the JINR Dubna. From a 1.25 h irradiation of a 12 mg/cm^2natNd₂O₃ target, we obtained 2.7 MBq of ¹⁴⁹Tb (70 µCi) at 20 min EOB. This allows the conclusion, that a dedicated cyclotron equipped with a modern ECR-ion source, providing high ion currents would allow the continuous production of batches of the order of 10–20 GBq of ¹⁴⁹Tb for routine RI-therapy.

The lower cross section of the spallation process can be compensated by using very thick targets. On-line mass separation technique provides high purity isotopically clean ¹⁴⁹Tb preparations, independently on the production route chosen. At the ISOLDE facility at CERN, we prepared batches of up to 500 MBq ¹⁴⁹Tb by combining on-line mass separation process followed by a cation exchange chromatography process using α-HIBA as eluent. The obtained ¹⁴⁹Tb preparations showed excellent behavior in labeling of chelated monoclonal antibodies.