Alpha-hydroxyisobutyric acid-assisted solid-liquid chromatography for the separation of lutetium-177 from neutron-irradiated natural ytterbium

Aulia Arivin Billah; Kukuh Eka Prasetya; Fany Triyatna; Daya Agung Sarwono; Abidin Abidin; Fernanto Rindiyantono; Maiyesni Maiyesni; Miftakul Munir; Indra Saptiama; Rien Ritawidya; Agustino Zulys

doi:10.1515/ract-2023-0234

Article

Alpha-hydroxyisobutyric acid-assisted solid-liquid chromatography for the separation of lutetium-177 from neutron-irradiated natural ytterbium

Aulia Arivin Billah , Kukuh Eka Prasetya , Fany Triyatna , Daya Agung Sarwono , Abidin Abidin , Fernanto Rindiyantono , Maiyesni Maiyesni , Miftakul Munir , Indra Saptiama , Rien Ritawidya and Agustino Zulys

Published/Copyright: February 6, 2024

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From the journal Radiochimica Acta Volume 112 Issue 3

Abstract

The production method of no-carrier added Lutetium-177 (¹⁷⁷Lu) was developed from a neutron-activated natural ytterbium (Yb) using column chromatography separation method. Dowex W50 X8 resin and a combination of alpha-hydroxyisobutyric acid (α-HIBA) and hydrochloric acid (HCl) were used as column filler and eluent, respectively. HCl increased the desorption and separation between ¹⁷⁷Lu and Yb at a concentration of 0.25 M, while the optimal α-HIBA concentration was 0.15 M, resulting in ¹⁷⁷Lu yield of 81.19 % and low impurities (¹⁷⁵Yb: 9.28 %, and ¹⁶⁹Yb: 2.09 %). Nevertheless, further study using an enriched ¹⁷⁶Yb target is essential to significantly increase the specific activity of ¹⁷⁷Lu.

Keywords: no-carrier added 177Lu; alpha hydroxyisobutyric acid; ion exchange chromatography; separation method

Corresponding author: Aulia Arivin Billah, Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, National Research and Innovation Agency (BRIN), Puspiptek Area, South Tangerang, 15314, Indonesia; and Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Indonesia, Depok, 16424, Indonesia, E-mail: auli004@brin.go.id

Acknowledgments

The research was supported by the Degree By Research Program - BRIN and Research Organization for Nuclear Energy, the National Research and Innovation Agency (ORTN-BRIN).

Research ethics: Not applicable.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: The authors state no conflict of interest.
Research funding: ORTN-BRIN, grants number TR-032.
Data availability: Not applicable.

References

1. Kristiansson, A., Örbom, A., Ahlstedt, J., Karlsson, H., Zedan, W., Gram, M., Åkerström, B., Strand, S. E., Altai, M., Strand, J., Timmermand, O. V. 177Lu‐psma‐617 Therapy in Mice, with or without the Antioxidant α1‐Microglobulin (A1m), Including Kidney Damage Assessment Using 99mTc‐mag3 Imaging. Biomolecules 2021, 11, 1.10.3390/biom11020263Search in Google Scholar PubMed PubMed Central

2. Humani, T. S., Sutari, S., Triningsih, T., Ramli, M., Ritawidya, R., Haryuni, R. D. Preparation of (177Lu-DOTA)n-PAMAM-[Nimotuzumab-F(ab’)2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancers Treatment. J. Math. Fundam. Sci. 2017, 49, 258; https://doi.org/10.5614/j.math.fund.sci.2017.49.3.4.Search in Google Scholar

3. Marganiec-Gałązka, J., Ziemek, T., Broda, R., Cacko, D., Czudek, M., Jęczmieniowski, A., Kołakowska, E., Lech, E., Listkowska, A., Saganowski, P., Tymiński, Z. Standardization of 177Lu by Means of 4π(LS)β-γ Coincidence and Anti-Coincidence Counting. J. Radioanal. Nucl. Chem. 2022, 331, 3283; https://doi.org/10.1007/s10967-022-08330-0.Search in Google Scholar

4. Emmett, L., Willowson, K., Violet, J., Shin, J., Blanksby, A., Lee, J. Lutetium-177 PSMA Radionuclide Therapy for Men with Prostate Cancer: A Review of the Current Literature and Discussion of Practical Aspects of Therapy. J. Med. Radiat. Sci. 2017, 64, 52–60; https://doi.org/10.1002/jmrs.227.Search in Google Scholar PubMed PubMed Central

5. Keam, S. J. Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Mol. Diagn. Ther. 2022, 26, 467; https://doi.org/10.1007/s40291-022-00594-2.Search in Google Scholar PubMed PubMed Central

6. Das, S., Al-Toubah, T., El-Haddad, G., Strosberg, J. 177Lu-DOTATATE for the Treatment of Gastroenteropancreatic Neuroendocrine Tumors. Expert. Rev. Gastroenterol. Hepatol. 2019, 13, 1023; https://doi.org/10.1080/17474124.2019.1685381.Search in Google Scholar PubMed PubMed Central

7. Lahiri, S., Nayak, D., Nandy, M., Das, N. R. Separation of Carrier Free Lutetium Produced in Proton Activated Ytterbium with HDEHP. Appl. Radiat. Isot. 1998, 49, 911; https://doi.org/10.1016/s0969-8043(97)10101-4.Search in Google Scholar

8. Zahn, G. S., Genezini, F. A., da Silva, P. S. C., Nory, R. M., Moreira, E. G., Santiago, P. S. On the Feasibility of Producing Lu-177 in the IEA-R1 Reactor via the Direct Route. Braz. J. Radiat. Sci. 2021, 9, 1; https://doi.org/10.15392/bjrs.v9i1a.1411.Search in Google Scholar

9. Soliman, M. A., Mohamed, N. M. A., Takamiya, K., Sekimoto, S., Inagaki, M., Oki, Y., Ohtsuki, T. Estimation of 47Sc and 177Lu Production Rates from Their Natural Targets in Kyoto University Research Reactor. J. Radioanal. Nucl. Chem. 2020, 324, 1099; https://doi.org/10.1007/s10967-020-07156-y.Search in Google Scholar

10. Boldyrev, P. P., Zagryadskii, V. A., Erak, D. Y., Kurochkin, A. V., Markovskii, D. V., Mikhin, O. V., Proshin, M. A., Khmyzov, N. V., Chuvilin, D. Y., Yashin, Y. A. Possibility of Obtaining High-Activity 177Lu in the IR-8 Research Reactor. At. Energy 2017, 121, 208; https://doi.org/10.1007/s10512-017-0185-4.Search in Google Scholar

11. Zhuo, L., Yang, Y., Yue, H., Xiong, X., Wang, G., Wang, H., Yang, L., Lin, Q., Chen, Q., Tu, J., Wei, H., Yang, X., Kan, W. Effective Lutetium/ytterbium Separation for No-Carrier Added Lutetium-177 Production. J. Radioanal. Nucl. Chem. 2022, 331, 5719; https://doi.org/10.1007/s10967-022-08588-4.Search in Google Scholar

12. Ambul, E. V., Goletskii, N. D., Medvedeva, A. I., Naumov, A. A., Puzikov, E. A., Afonin, M. A., Shishkin, D. N. Separation of Ytterbium And Lutetium with Solutions of (2-Ethylhexyl)Phosphonic Acid Mono-2-Ethylhexyl Ester in Hydrocarbons from Nitric Acid Solutions and its Simulation. Radiochemistry 2022, 64, 300; https://doi.org/10.1134/s1066362222030067.Search in Google Scholar

13. Kuznetsov, R. A., Bobrovskaya, K. S., Svetukhin, V. V., Fomin, A. N., Zhukov, A. v. Production of Lutetium-177: Process Aspects. Radiochemistry 2019, 61, 381; https://doi.org/10.1134/s1066362219040015.Search in Google Scholar

14. Hashimoto, K., Matsuoka, H., Uchida, S. Production of No-Carrier-Added 177Lu via the 176Yb(n,γ)177Yb→177Lu Process. J. Radioanal. Nucl. Chem. 2003, 255, 177.Search in Google Scholar

15. Nguyen, N. T., Duong, V. D., Bui, V. C., Pham, T. M., Nguyen, T. H. Study on the Production of 177Lu for Medical Purposes at the Dalat Research Reactor. Part 1. Study on Production of 177Lu at the Dalat Research Reactor. Nucl. Sci. Technol. 2015, 5, 18; https://doi.org/10.53747/jnst.v5i1.181.Search in Google Scholar

16. Kumar, P., Jaison, P. G., Rao, D. R. M., Telmore, V. M., Sarkar, A., Aggarwal, S. K. Determination of Lanthanides and Yttrium in High Purity Dysprosium by Rp-Hplc Using δ-hydroxyisobutyric Acid as an Eluent. J. Liq. Chromatogr. Relat. Technol. 2013, 36, 1513; https://doi.org/10.1080/10826076.2012.692148.Search in Google Scholar

17. Kim, A., Choi, K. Preparative Chromatographic Separation of Neighboring Lanthanides Using Amines as a pH Adjusting Additive for Producing Carrier-free 177Lu. J. Radioanal. Nucl. Chem. 2022, 331, 1451; https://doi.org/10.1007/s10967-022-08216-1.Search in Google Scholar

18. Pourjavid, M. R., Norouzi, P., Rashedi, H., Ganjali, M. R. Separation and Direct Detection of Heavy Lanthanides Using New Ion-Exchange Chromatography: Fast Fourier Transform Continuous Cyclic Voltammetry System. J. Appl. Electrochem. 2010, 40, 1593; https://doi.org/10.1007/s10800-010-0144-4.Search in Google Scholar

19. Watanabe, S., Hashimoto, K., Watanabe, S., Iida, Y., Hanaoka, H., Endo, K., Ishioka, N. S. Production of Highly Purified No-Carrier-Added 177Lu for Radioimmunotherapy. J. Radioanal. Nucl. Chem. 2015, 303, 935; https://doi.org/10.1007/s10967-014-3534-y.Search in Google Scholar

20. Pasqualini Da Silva, G., Alberto, J., Junior, O. Study of the Production of 177Lu through 176Yb (n, γ) 177Yb → 177Lu Nuclear Reaction. Dissertation, Sao Paulo University, 2008; pp. 1–78.Search in Google Scholar

21. Li, F. F., Cui, W. R., Jiang, W., Zhang, C. R., Liang, R. P., Qiu, J. D. Stable Sp2 Carbon-Conjugated Covalent Organic Framework for Detection and Efficient Adsorption of Uranium from Radioactive Wastewater. J. Hazard. Mater. 2020, 392; https://doi.org/10.1016/j.jhazmat.2020.122333.Search in Google Scholar PubMed

22. Jun, B. M., Lee, H. K., Park, S., Kim, T. J. Purification of Uranium-Contaminated Radioactive Water by Adsorption: A Review on Adsorbent Materials. Sep. Purif. Technol. 2022, 278, 119675; https://doi.org/10.1016/j.seppur.2021.119675.Search in Google Scholar

23. Zhang, M., Gu, P., Zhang, Z., Liu, J., Dong, L., Zhang, G. Effective, Rapid and Selective Adsorption of Radioactive Sr2+ from Aqueous Solution by a Novel Metal Sulfide Adsorbent. Chem. Eng. J. 2018, 351, 668; https://doi.org/10.1016/j.cej.2018.06.069.Search in Google Scholar

24. Park, H., Kwon, D. H., Cha, Y. H., Kim, T. S., Han, J., Ko, K. H., Jeong, D. Y., Kim, C. J. Stable Isotope Production of 168Yb and 176Yb for Industrial and Medical Applications. J. Nucl. Sci. Technol. 2008, 45, 111; https://doi.org/10.1080/00223131.2008.10875990.Search in Google Scholar

25. Park, H., Kostritsa, S., Kwon, D., Cha, Y., Lee, K., Nam, S., Han, J., Rhee, Y., Kim, C.-J. Effect of Laser Intensity on the Selective Photoionization of the 168Yb Isotope. J. Korean Phys. Soc. 2002, 41, 3.Search in Google Scholar

26. Karadag, M., Yücel, H. Measurement of Thermal Neutron Cross-Section and Resonance Integral for the 174Yb(n,γ) 175Yb Reaction by the Cadmium Ratio Method. Nucl. Instrum. Methods Phys. Res. B 2008, 266, 2549; https://doi.org/10.1016/j.nimb.2008.03.201.Search in Google Scholar

27. Zaved, M. M., Islam, M. A., Hossain, A. Experimental Cross Sections of the 174Yb(n,γ) 175Yb Reaction at New Energies of 0.0334 eV and 0.0536 eV. Radiat. Phys. Chem. 2020, 166, 108471; https://doi.org/10.1016/j.radphyschem.2019.108471.Search in Google Scholar

28. Wang, Q., Gao, F., Yang, L., Shi, T., Xie, Q. Study of the Thermodynamic Behavior of Rare Earths in the System of R-SO3H α-HIBA on HPLC and its Application to Analytical Chemistry. Microchem. J. 1995, 52, 236; https://doi.org/10.1006/mchj.1995.1092.Search in Google Scholar

29. Ansari, S. A., Mohapatra, P. K., Manchanda, V. K. A Novel Malonamide Grafted Polystyrene-Divinyl Benzene Resin for Extraction, Pre-Concentration and Separation of Actinides. J. Hazard. Mater. 2009, 161, 1323; https://doi.org/10.1016/j.jhazmat.2008.04.093.Search in Google Scholar PubMed

30. Wakaki, S., Tanaka, T. Stable Sm Isotopic Analysis of Terrestrial Rock Samples by Double-Spike Thermal Ionization Mass Spectrometry. Int. J. Mass Spectrom. 2016, 407, 22; https://doi.org/10.1016/j.ijms.2016.06.010.Search in Google Scholar

31. Cáceres-Rivero, C., Ramos-Trujillo, B. J., Farfán, Y., Solis, J. L., Bedregal, P. The Role of pH in the Separation of Lu and Yb by Ion-Exchange Explained by Novel Chemical Structures of Lanthanide Complexes. Results Chem. 2022, 4, 100514; https://doi.org/10.1016/j.rechem.2022.100514.Search in Google Scholar

32. Balasubramanian, P. S. Separation of Carrier-Free Lutetium-177 From Neutron Irradiated Natural Ytterbium Target. J. Radioanal. Nucl. Chem. 1994, 185, 2; https://doi.org/10.1007/bf02041303.Search in Google Scholar

33. Barkhausen, C. Production of Non Carrier Added (n.c.a.) 177Lu for Radiopharmaceutical Applications. Dissertation, Technical University Munich: Munich, 2011; pp. 1–120.Search in Google Scholar

34. Dembowski, M., Rowley, J. E., Boland, K., Droessler, J., Hathcoat, D. A., Marchi, A., Goff, G. S., May, I. Rare Earth Element Separations by High-Speed Counter-current Chromatography. J. Chromatogr. A 2022, 1682, 463528; https://doi.org/10.1016/j.chroma.2022.463528.Search in Google Scholar PubMed

35. Dembiński, W., Poniński, M., Fiedler, R. Preliminary Results of the Studies on Fractionation of Ytterbium Isotopes in Yb(III)-acetate/Yb-amalgam System. Sep. Sci. Technol. 1998, 33, 1693; https://doi.org/10.1080/01496399808545074.Search in Google Scholar

36. Salek, N., Shirvani Arani, S., Bahrami Samani, A., Vosoghi, S., Mehrabi, M. Feasibility Study for Production and Quality Control of Yb-175 as a Byproduct of No Carrier Added Lu-177 Preparation for Radiolabeling of DOTMP. Australas. Phys. Eng. Sci. Med. 2018, 41, 69; https://doi.org/10.1007/s13246-017-0611-x.Search in Google Scholar PubMed

37. Baek, J., Schwahn, A. B., Lin, S., Pohl, C. A., De Pra, M., Tremintin, S. M., Cook, K. New Insights into the Chromatography Mechanisms of Ion-Exchange Charge Variant Analysis: Dispelling Myths and Providing Guidance for Robust Method Optimization. Anal. Chem. 2020, 92, 13411; https://doi.org/10.1021/acs.analchem.0c02775.Search in Google Scholar PubMed

38. Kondev, F. G., Wang, M., Huang, W. J., Naimi, S., Audi, G. The NUBASE2020 Evaluation of Nuclear Physics Properties*. Chinese Phys. C 2021, 45, 030001; https://doi.org/10.1088/1674-1137/abddae.Search in Google Scholar

39. Lakka, N. S., Kuppan, C. Principles of chromatography method development. Biochem. Anal. Tools 2019, 89501, 1.Search in Google Scholar

Received: 2023-09-26

Accepted: 2023-12-14

Published Online: 2024-02-06

Published in Print: 2024-03-25

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Keywords for this article

no-carrier added 177Lu; alpha hydroxyisobutyric acid; ion exchange chromatography; separation method