Radiopharmaceuticals are medicinal formulations containing radioisotopes which are used for diagnosis or therapy. Radiopharmaceuticals based on radioactive terbium (Tb) isotopes can be used for radiotherapy, where a specific tumor is targeted and selectively irradiated. One of these isotopes is terbium-161 (161Tb), a beta emitter, and can be produced in the Belgian Reactor 2 (BR2) at SCK•CEN.
The 161Tb isotope can be synthesized by irradiation of gadolinium-160 (160Gd) targets: when a neutron is captured by 160Gd this yields 161Gd which decays to 161Tb. Since the intermediate 161Gd is short-lived, it will already have disappeared when the target is unloaded from the reactor. In addition, part of the produced 161Tb will have decayed to the stable isotope 161Dy. Therefore, to isolate and purify 161Tb from the dissolved irradiated 160Gd targets, a method must be developed to separate Tb from the other lanthanide elements (mainly the Gd matrix) and impurities.
Due to the similarity in chemical properties, the separation of adjacent lanthanides is highly challenging. A well-known column separation method using a cation exchange resin with α-hydroxyisobutyric acid (α-HIBA) as eluent has been used to isolate 161Tb from milligram amounts of 160Gd. This is one of the most efficient separation methods known for the separation of adjacent lanthanides. There are however several downsides to this separation process: (i) the duration of this separation is rather long, (ii) a complete separation cannot be achieved when a small amount of 161Tb has to be isolated from a lanthanide matrix and as a result one can only obtain part of the available 161Tb as a pure fraction and (iii) with increasing target size, the pure 161Tb fraction decreases due to severe peak broadening and increased tailing. Because of these important disadvantages, especially when larger targets have to be processed, a new and improved separation method needs to be developed to produce considerable amounts of 161Tb for radiopharmaceutical use.
The proposed strategy in this doctoral research is to dissolve the irradiated targets and selectively oxidize Tb(III) into Tb(IV) prior to the separation process. The high chemical stability of Tb(III) requires strong oxidizing agents to form Tb(IV). Therefore the objective is to develop an electrochemical method to oxidize Tb(III) to Tb(IV). Since the applied current is used to oxidize Tb(III), no additional chemicals need to be used and a higher level of control can be achieved over the oxidation process. Several electrochemical techniques such as cyclic voltammetry and chronoamperometry will be subject to this investigation. Chemical analysis of the oxidation efficiency will be performed with techniques such as UV/VIS spectroscopy. The stability of the formed Tb(IV) will also be studied together with other parameters of influence to the successive separation method. Once the oxidation method is established and optimised, the second part of the project will be devoted to develop a Tb(IV)/Gd(III) separation protocol based on column chromatography.