Actinium-225 Separation

 

 

²²⁵Ac is a promising therapeutic nuclear medicine radionuclide. Applications include direct treatment with ²²⁵Ac conjugated to biolocalization agents and the use of ²²⁵Ac as a source of ²¹³Bi. There are several processes available for the production of ²²⁵Ac, including decay of ²²⁹Th obtained from aged ²³³U breeder reactor fuel (Figure 1) and proton spallation on ²³²Th targets. [1-11]

Both of these methods require separation of ²²⁵Ac and ²²⁵Ra from relatively large amounts of Th (5-50 grams). ²²⁵Ra, the immediate parent of ²²⁵Ac can be used as a source for additional ²²⁵Ac after a short period of ingrowth. The production of ²²⁵Ac from ²²⁵Ra is particularly important for the ²³²Th spallation route, as a source of ²²⁵Ac without the long lived ²²⁷Ac impurity contained in the ²²⁵Ac produced directly from spallation (Figure 2). [1, 4 6-11]

 

 

 

 

 

There are two main routes for separation of the large mass of Th from the Ac and Ra: 1) dissolution in HNO₃ -HF and selective extraction of Th (rejecting Ac/Ra) [1,2,4,6,11] and 2) complexation of Th with sulfate or citrate to form anionic complexes and selective extraction of Ac and Ra by cation exchange resin. [7-10]

In route 1, Th is dissolved in HNO₃ with a trace amount of HF to speed and complete dissolution of thorium metal. Th is then extracted by solvent extraction with organophosphorus extractants, such as diamyl(amyl)phosphonate (DAAP), or chromatography using gel type or macroporous anion exchange resins (Figure 3). The gel type resins offer higher capacity than the macroporous materials (1.7-2.0 vs 1.0-1.5 meq/mL), while the macroporous resins exhibit higher physical stability and resistance to shrinking and swelling while cycling from the high HNO₃ (6-8 M) during loading of Th and low HNO₃ (0.01 – 0.05 M) during recovery of Th.

Because a large mass of Th is being extracted (5-50 grams), several solvent extraction stages (3 stages of 1-2 L of 0.5M DAAP) or relatively large columns of anion exchange resin (1-2 L) are required for near complete extraction of Th. High concentrations of HNO₃ (~8M) are required for efficient retention of Th by anion exchange, and large volumes of eluate (1-2 L) are required to pass the Ac and Ra through the large anion exchange columns. Therefore, evaporation of the Ac/Ra fraction may be required to reduce the HNO₃ concentration and volume prior to subsequent ²²⁵Ac/Ra purification steps.

In route 2, preparation of the thorium source material for selective extraction of Ac and Ra may also begin with the dissolution of thorium metal with HNO₃-HF or HCl-HF, evaporation and redissolution in ammonium citrate or H₂SO₄ or by direct dissolution by H₂SO₄-HF. [8.9,12-15] From sulfate or citrate, under the correct conditions, Ac and Ra can be selectively extracted onto 50Wx8 gel-type cation exchange resin, while anionic Th species are rejected (Figure 3).

Dissolution of Th metal by H₂SO₄-HF is slower than dissolution in HNO₃-HF, but avoids evaporation steps. The Th metal is first converted to a fluffy white Th(SO₄)_x powder with warm H₂SO₄ with a trace of HF (Figure 4). Upon cooling and diluting the solution with water, the Th(SO₄)_x dissolves.

The selective extraction of Ac and Ra while rejecting the large mass of Th, allows the use of relatively small columns of cation exchange resin (50-100 mL). After rinsing to provide additional decontamination from Th, the Ac and Ra are recovered with 150 – 300 mL of 5-6M HNO₃, which can be directly processed by the subsequent separation processes without evaporation or feed adjustment (Figure 5).

Following removal of the bulk Th, the Ac/Ra fraction is further purified by ion exchange and extraction chromatography to remove any remaining traces of Th or spallation or decay byproducts (Figure 5C-5D). Further purification methods include anion exchange and UTEVA resin for additional Th removal and removal of spallation byproducts (Pa, U, Po) and DGA normal resin for the separation of Ac and Ra and removal of spallation byproducts (La, Ce, Po, Ba, Sr, etc…) and reagent impurities (Al, Fe, Ca, etc…). [8,9,16]

Ultimately, in many ²²⁵Ac production methods, ²²⁵Ac is purified and concentrated using DGA resin and recovered in dilute HCl. One important impurity that must be considered for separations on DGA resin is calcium. When loading DGA from 1-3M HNO₃ and stripping with dilute HCl, Ca will co-elute with Ac (Figure 6). Therefore, rinses of the DGA resin with 9M HCl or 8M HNO₃ are needed to remove Ca impurities (Figure 7). [9]

In the spallation production route, rare earth impurities, such as ¹⁴⁰La(¹⁴⁰Ba), ¹³⁹Ce, ¹⁴¹Ce, and ¹⁴⁴Ce, are produced. These rare earth impurities must be separated from ²²⁵Ac fraction. One effective method for the group separation of rare earth metal ions from Ac is elution from DGA, normal with 9-10 M HNO₃ (Figure 6). [7] At the high HNO₃ concentration, the retention of Ac decreases, while the retention of rare earth metal ions remains high. The Ac fraction, in 9-10 M HNO₃, can then be diluted to 6-8M HNO₃ and processed through another DGA, normal cartridge to concentrate the Ac and convert to dilute HCl (Figure 5).

References

1] Aliev, R.A., Ermolaev, S.V., Vasiliev, A.N., Ostapenko, V.S., Lapshina, E.V., Zhuikov, B.L., Zakharov, N.V., Pozdeev, V.V., Kokhanyuk, V.M., Myasoedov, B.F., Kamykov, S.N. 2014. Isolation of Medicine-Applicable Actinium-225 from Thorium Targets Irradiated by Medium Energy Protons. Solv. Extr. Ion. Exch. 32(5), 468-477.

2] Boll, R.A., Malkemus, D., Mirzadeh, S. 2005. Production of Ac-225 for alpha particle therapy. Appl. Radiat. Isot. 62, 667-679.

3] Bond, A.H., Horwitz, E.P., McAlister, D.R., 2006. A Multicolumn Selectivity Inversion Generator for the Production of High Purity Actinium-225 for Use in Therapeutic Nuclear Medicine, United States patent number 7,087,206. (Licensed to Northstar Medical Radioisotopes)

4] Ermolaev, S.V., Zhuikov, B.L., Kokhanyuk, V.M., Matushko, V.L., Kalmykov, S.N., Aliev, R.A., Tananaev, I.G., Myasoedov, B.F. 2012. Production of actinium, radium, and thorium isotopes from natural thorium irradiated with protons up to 141 MeV. Radiochim. Acta. 100, 223-229.

5] Harvey, J.H., Nolen, J.A., Kroc, T., Gomes, I., Horwitz, E.P., McAlister, D.R. 2009. Alternative Methods for the Production of Ac-225. 10th International Symposium of the International Isotope Society, Chicago, IL, June 14-18.

6] Harvey, J.H., Nolen, J., Vandergrift, G., Kroc, T., Gomes, I., McAlister D.R., Horwitz, E.P. 2011. Production of Actinium-225 via High Energy Proton Induced Spallation on Thorium-232. Final Technical Report DE-SC0003602. https://www.osti.gov/scitech/servlets/purl/1032445/

7] Mastren, T., Radchenko, V., Owens, A., Copping, R., Boll, R., Griswold, J.R., Mirzadeh, S., Wyant, L.E., Brugh, M., Engle, J.W., Nortier, F.M., Birnbaum, E.R, John, K.D., Fassbender, M.E. 2017. Simultaneous Separation of Actinium and Radium Isotopes from a Proton Irradiated Thorium Matrix. Nature Scientific Reports, 7, 8216. doi:10.1038/s41598-017-08506-9

8] McAlister, D.R., Horwitz, E.P. 2018. Selective Separation of Radium and Actinium from Bulk Thorium Target Material on Strong Acid Cation Exchange Resin from Sulfate Media, Applied Radiation and Isotopes, 140, 18-23.

9] McAlister, D.R., Horwitz, E.P., Perron, R., Gendron, D., Causey, P., Harvey, J.T., “Selective Separation of Radium and Actinium from Bulk Thorium Target Material,” 11th International Symposium on Targeted Alpha Therapy, Ottawa, Ontario, Canada, April 1-4, 2019.

10] Radchenko, V., Engle, J.W., Wilson, J.J., Massen, J.R., Nortier, F.M., Taylor, W.A., Birnbaum, E.R., Hudston, L.A., John, K.D., Fassbender, M.E., 2015. Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes, J. Chromatogr. A. 1380, 55-63.

11] Zhuikov, B.L., Kalmykov, S.N., Ermolaev, S.V., Aliev, R.A., Kokhanyuk, V.M., Matushko, V.L., Tananaev, I.G., Myasoedov, B.F. 2011. Production of 225Ac and 225Ra by Irradiation of Th with Accelerated Protons. Radiochemistry, 53(1), 73-80.

12] Allen, K.A., McDowell, W.J. 1963. The Thorium Sulphate Complexes from Di-n-decylamine Sulphate Extraction Equilibria. J. Phys. Chem. 67, 1138-1140.

13] Keskar, M., Kasar, U.M., Singh Mudher, K.D., 2000. Solid State Reactions of UO2, ThO2 and their Mixed Oxides with Sulphates of Potassium, J. Nucl. Mater. 282, 146-151.

14] Zebroski, E.L., Alter, H.W., Heumann, F.K. 1951 Thorium Complexes with Chloride, Fluoride, Nitrate, Phosphate and Sulfate. J. Am. Chem. Soc. 73(12), 5646-5650.

15] Ziehlen, A.J. 1959. Thermodynamics of the Sulfate Complexes of Thorium. J. Am. Chem. Soc., 81(19), 5022-5028.

16] Horwitz, E.P., McAlister, D.R., Bond, A.H., Barrans, Jr., R.E. 2005. Novel Extraction Chromatographic Resins Based on Tetraalkyldiglycolamides: Characterization and Potential Applications. Solv. Extr. Ion Exch., 23, 319-344.