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Supported ionic liquid phases for extraction and separation of medical radiolanthanides - Towards purification of medical samarium-153

Book - Dissertation

Radiolanthanides are gaining more importance in nuclear medicine because of their favorable decay characteristics. The emission of beta particles with energies suitable to destroy malicous tumor cells is very useful in cancer therapy, whereas the emission of gamma photons can be used for diagnostic purposes. Some radiolantanides are even able to serve both purposes concurrently (theranostics) making it possible to follow the effectiveness of the therapy in situ. Radiolanthanides have the potential to be deployed in a wide variety of applications in nuclear medicine. Because of the very similar chemical properties across the lanthanide series, different radiolanthanides can be linked to the same chelator. This makes them easily interchangeable, by which radiopharmaceuticals can be tailored to serve a specific purpose. Selecting the most proper particle emission energy for therapy is important to keep radiation damage to healthy tissue and vital organs as low as possible. This way, a high tumor-to-normal tissue absorbed dose can be assured. However, the very similar chemical properties also imply that separation of two neighboring lanthanides is very challenging, and is one of the main challenges in the production of radiolanthanides for medical applications. Radiolanthanides are most efficiently produced in a nuclear research reactor via neutron irradiation, which involves the bombardment of an enriched target with neutrons. Depending on the production strategy followed, the obtained radiolanthanide is carrier-added or non-carrier-added. The product resulting from each production pathway might require a purification step for different reasons before being used in a radiopharmaceutical. Isolation of non-carrier-added radiolanthanides from their target material results in a product with high specific activity, which is highly suitable for targeted radiotherapy. Carrier-added-produced radiolanthanides cannot be separated from their target material, and thus will have limited specific activities only. Therefore, they are not applied in targeted radiotherapy, but are found to be very suitable for bone pain palliation, radiation synovectomy and imaging. During neutron irradiation, long-lived radionuclidic impurities might be produced concurrently, impeding the medicinal use of the carrier-added radiolanthanide and limiting its shelf-life. After all, background radiation levels of the patient have to be limited, and are strictly regulated. A purification step for these radiolanthanides might thus be required to achieve adequate radionuclidic purity. The use of a certain radiopharmaceutical in nuclear medicine is highly dependent on the availability of the radiolanthanide of interest, its decay characteristics and its achievable specific activity. Therefore, a lot of research has been conducted to find suitable purification and isolation methods for medical radiolanthanides produced in nuclear research reactors. A comprehensive overview for nuclear-reactor-produced medical radiolathanides is given within the framework of this research project. In this PhD dissertation, a new and innovative approach for the separation of samarium and europium towards the purification of medical Sm-153 is presented. Sm-153 serves well in nuclear medicine because of its favorable decay characteristics, i.e. a very manageable physical half-life of 46.284 h and the emission of beta particles with a mean energy of 233 keV, which is suitable for radiotherapy. The simultaneous emission of gamma photons of 103.2 keV can be used for imaging, making Sm-153 suitable for diagnosis and theranostics. Sm-153 is produced carrier-added in a nuclear research reactor. Long-lived Eu-154 impurities are produced concurrently, limiting the use of Sm-153 radiopharmaceuticals. Separation of Sm(IIi) and Eu(III) is challenging because of their very similar chemical properties. A change in valence state induces a significant change in chemical properties, leading to possibilities for a more efficient separation. Reduction of Eu(III) to its divalent state is the most easy to achieve in the lanthanide series because of its electron configuration. Reduction of Eu(III) was already well-studied before in media stable to reduction, like aqueous chloride solutions. However, in this dissertation it is shown that reduction of Eu(III) is also possible in aqueous nitrate media, and that Eu(II) remains relatively stable in these media. Nevertheless, high nitrate salt concentrations are needed to achieve this reduction and stability. These high nitrate salt concentrations also proved to be very advantageous in the separation step, making use of the salting-out principle. A solvent extraction method making use of Aliquat 336 nitrate ([A336][NO3]) as the organic phase was developed to selectively extract Sm(III), leaving Eu(II) in the aqueous phase. This promising and highly efficient separation method for samarium and europium was further developed towards an extraction chromatography method. In this approach, [A336][NO3] was immobilized on a solid support, i.e. a supported ionic liquid phase (SILP). Extraction chromatography already proved to be very useful in radiochemical processing of medical radionuclides because of its easiness of operation, its ability to achieve high separation efficiencies and its automation possibilities. Moreover, any processing problems caused by the high viscosity of neat [A336][NO3] could be avoided. Based on the solvent extraction step, Sm(III) was extracted to the ionic liquid layer of the SILP when using a concentrated nitrate salt solution as mobile phase. In these conditions, Eu(II) was not retained by the SILP when passing through the column material. Sm(III) could be easily removed from the SILP material by the use of water, reducing the salt concentration in the system. This way, the samarium-rich fraction contains less nitrate salts, which is beneficial for further radiopharmaceutical processing.
Publication year:2019
Accessibility:Open