Production routes of the alpha emitting 149Tb for medical application

Abstract

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/cm2 natNd2O3 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.