Short project description
Radiopharmaceuticals are medical formulations that consist of a radionuclide, a linker and a targeting vector. They can be applied in nuclear medicine for therapy to destroy the harmful cancer cells via the emission of energetic particles, or for diagnosis (imaging) to visualize the infected areas via the emission of photons. Depending on the chosen radionuclide, some radiopharmaceuticals can be used for both therapy and diagnosis (theranostics). Over the last decades, the interest for lutetium-177 (177Lu) in nuclear medicine has grown exponentially because of its favorable decay characteristics. A half-life of 6.65 days, the simultaneous emission of low to medium energy β– particles and γ photons allows for theranostic use. If the targeting vector is able to bind to a very specific receptor site in a harmful cancer cell, a radiopharmaceutical can be developed for targeted radionuclide therapy (endoradiotherapy, TRNT). To be efficient, this technique requires a high purity and high specific activity of the 177Lu radionuclide as only a limited number of receptor sites are available in the cancer cell, and targeting vectors are expensive.
177Lu can be produced most efficiently via neutron activation in a nuclear reactor like the Belgian Reactor 2 (BR2) at SCK•CEN.1 In general, two different production strategies exist. In a first one, a natural or enriched 176Lu target is irradiated with neutrons to form 177Lu with high yield. However, the specific activity of the resulting 177Lu will remain limited, as both isotopes cannot be chemically separated. The redundant 176Lu will remain present in the radiopharmaceutical. In a second production strategy, highly enriched 176Yb can be irradiated with neutrons to form 177Yb, which is an unstable isotope with a half-life of 1.911 h. Subsequent β– decay delivers the 177Lu for radiotherapy. 177Lu can be separated from the 176Yb target material and other impurities via radiochemical processing, resulting in a very high specific activity for 177Lu. Additionally, efficient recovery of the valuable 176Yb target material to be used in a next irradiation campaign is possible.
Because of the very similar chemical properties of two adjacent lanthanides, isolation of 177Lu from 176Yb is highly challenging. Moreover, minor amounts of 177Lu have to be separated from high amounts of 176Yb. Most of the current separation techniques make use of the small differences in ligand interactions, which often requires multiple separation steps or long separation times. One of the most efficient separation techniques for separation of two adjacent lanthanides known today is the use of an extraction chromatography resin in combination with an α-hydroxyisobutiric acid (α-HIBA) aqueous eluent. The process was optimized for Yb/Lu separation in 2005 by Horwitz et al. by the addition of a secondary separation step using a diglycolamide (DGA) containing resin for concentration and acid adjustment. This second step avoids lengthy evaporations and acidity adjustments between successive extraction chromatography runs.2,3 However, separation factors that can be achieved by passing through the tandem column setup only once remain relatively low. Therefore, the entire procedure still includes several tandem column runs to arrive at a reasonable radionuclidic purity and decontamination factor.
In the proposed PhD project, a new and innovative separation process will be developed combining a redox and extraction process. In a first step, ytterbium will be reduced to its divalent state, by which its chemical properties are changed considerably. This leads to possibilities for a more efficient separation method. However, Yb(II) has a highly oxidizing nature, by which it is difficult to stabilize in aqueous media. Therefore, reduction of Yb(III) to Yb(II) using different solvents and reduction techniques will be subject to this investigation. Electrochemical screening studies by means of cyclic voltammetry are a first major part of the research. Additionally, the stability of the formed Yb(II) species will be studied using UV-Vis and X-ray absorption fine structure (XAFS) spectroscopy. In subsequent steps, the separation possibilities using various solvometallurgical systems and the impact of different extraction parameters will be studied. Conventional analysis techniques (e.g. ICP-OES and ICP-MS) and spectrometric analysis techniques (e.g. gamma spectrometry) will be used to determine the extraction efficiency.