PhD Defense | Hongshan Zhu | Carbon materials tailored for Ac-225/Bi-213 separation and their use in radionuclide generators

Carbon materials tailored for ²²⁵Ac/²¹³Bi separation and their use in radionuclide generators

Cancer is a significant public health issue and one of the leading causes of death worldwide. Accordingly, developing effective cancer treatment strategies is of critical importance. One such approach involves targeted alpha therapy, owing to its high cytotoxic effects on cancer cells and minimal damage to surrounding healthy cells. Bismuth-213 (²¹³Bi), with unique radionuclide properties, is a promising candidate for targeted alpha therapy. ²¹³Bi is typically produced from the decay of ²²⁵Ac and is subsequently separated by radionuclide generators. Radionuclide generators can provide medical radionuclides locally, within hospitals, to reduce the ongoing need for a dedicated production facility. However, the current adsorbents used in the ²²⁵Ac/²¹³Bi generators limit the separation of a sufficient quantity of ²¹³Bi from ²²⁵Ac (e.g., > 4 GBq) for clinical applications. Chapter 1 presents the limitations and requirements of sorbents for ²²⁵Ac and ²¹³Bi separation. This thesis describes the design and investigation of alternative sorbents for ²²⁵Ac/²¹³Bi radionuclide generators.

Carbon materials with polycyclic aromatic rings typically exhibit high radiation resistance and considerable chemical stability under highly acidic conditions (e.g., pH < 2), and have already been widely used in radionuclide separation. As far as is known, there are currently no reports regarding the use of carbon materials or their derivatives to separate ²²⁵Ac and ²¹³Bi. Typically, carbon materials possess insufficient functional groups due to the decomposition of heteroatoms, such as oxygen and hydrogen, at elevated temperatures. However, grafting functional groups directly onto carbon materials can tune the interaction mechanism of ²²⁵Ac and ²¹³Bi, thereby improving the sorption capacity and separation factors of the isotope of interest. Carbon materials that have undergone direct grafting are expected to exhibit higher radiation stability than those subjected to indirect graftings, such as impregnation with extractants or the use of organic linkers.

This thesis reports on the preparation of various carbon materials—including activated carbon (in Chapter 3), irregular carbon materials (in Chapter 5), and spherical carbon beads (Chapter 6)— via sulfonation and oxidization treatments, with the goal of grafting sufficient active sorption sites for use in ²²⁵Ac and ²¹³Bi separation. The prepared samples were thoroughly characterized utilizing numerous techniques, including SEM, XRD, N₂ adsorption-desorption, TGA-MS, XPS, DRIFT, XPS, elemental analysis, etc. Batch experiments and column chromatography were used to investigate the separation performance of these materials.

The investigation of sulfonation conditions—including the sulfonation temperature from 80 to 190 °C, the sulfonation time from 3 to 6 hours, and the mass of the activated carbon to the volume of the concentrated sulfuric acid—is reported in Chapter 3. Substantial amounts of oxidized sulfur- and oxygen-containing groups were grafted on the sulfonated activated carbon. The specific surface area decreased due to the high density of functional groups, increased carbon sheet stacking, and the possible structural damage induced by the high oxidation process. Additionally, oxidized activated carbon was synthesized as a reference to confirm the main sorption active sites, revealing the oxygen-containing groups to be the primary active sorption sites for La³⁺, Ac^3+, and Bi³⁺. La³⁺ was confirmed as a surrogate for Ac³⁺ regarding the sorption behaviors onto the carbon materials with the oxidized sulfur- and oxygen-containing groups. Based on the sorption and desorption properties of La³⁺/Ac³⁺/Bi³⁺, the surface-modified activated carbon exhibited a high preference for the inverse generators compared to the direct generators.

The gamma radiation stability of the sulfonated activated carbon materials and the optimal material AG MP-50 resin was investigated, as discussed in Chapter 4. Compared to the AG MP-50 resin, the surface-modified activated carbon materials exhibited higher radiation stability regarding the active sorption sites, materials structures, and morphologies. This indicates that the surface-modified activated carbon materials could separate ²¹³Bi from ²²⁵Ac in an inverse generator.

The optimal carbon structures are discussed in Chapter 5. Suitable surface-modified carbon materials were chosen, which were beneficial for evaluating ²¹³Bi using a dilute HCl solution concentration (e.g., 1 M HCl). A high ²¹³Bi yield (e.g., 94%) with less than 0.04% ²²⁵Ac impurity could be obtained from the inverse generator. The AG MP-50 resin could further be used in a guard column to purify the ²¹³Bi eluate from the surface-modified carbon column. The proof of concept of a multi-column selective ²²⁵Ac/²¹³Bi inverse generator was established using the surface-modified carbon material in the primary column and AG MP-50 in the guard column. Different particle sizes of irregular surface-modified carbon particles were classified using a sieving technique for potential use in the inverse generators.

However, spherical particles are a preferred choice for column chromatography. The synthesis route for spherical surface-modified carbon beads by pyrolysis of the spherical cellulose beads and following sulfonation or oxidization treatments was preliminarily investigated, as described in Chapter 6. The separation performance of these spherical surface-modified carbon beads for La³⁺/Bi³⁺ was undiminished. This indicates that the spherical surface-modified carbon beads could be used in the inverse generators for the ²²⁵Ac and ²¹³Bi separation.

In addition to sulfonic acid and carboxylic groups, phosphate groups were also investigated for ²²⁵Ac and ²¹³Bi separation, as discussed in Chapter 7. Commercially available bis(2-ethylhexyl) phosphate (BEHP) modified activated carbon was used as an example to explore the La³⁺ and Bi³⁺ separation mechanism. The phosphate groups adsorbed La³⁺ by electrostatic attraction and surface complexation, and the adsorption capacity was very sensitive to the pH conditions. Results showed that the phosphate groups have a potential application in ²²⁵Ac and ²¹³Bi separation; however, further studies, including column tests, are required via suitable eluents.

Overall, the studies reported herein validated the use of surface-modified carbon materials for the separation of high-activity ²¹³Bi from ²²⁵Ac (e.g., > 4 GBq) in inverse generators. Furthermore, the AG MP-50 resin was identified as an effective sorbent for subsequent ²¹³Bi purification. An automated system for multi-column invest generator setups is expected to be implemented to supply ²¹³Bi in radiopharmaceutical applications. This work also elucidated the separation mechanisms of three acidic functional groups: sulfonic acid, phosphate, and carboxylic acid. This comprehensive insight could guide future improvements in ²²⁵Ac and ²¹³Bi separation technologies and potentially open up new avenues for research.

 

Promotor:

• Koen Binnemans (KULEUVEN)

Co-Promotor:

• Thomas Cardinaels (KULEUVEN/SCK CEN)
• Steven Mullens (VITO)

SCK CEN mentors:

• Stephan Heinitz (SCK CEN)

 

Click here for a list of obtained PhD degrees.