Materials
Hydrochloric acid (ultra-pure, 10 M) was purchased from Kanto Chemical Corporation (Tokyo, Japan). Ammonium acetate solution (10 M) was obtained from Nacalai Tesque (Kyoto, Japan). Ammonium solution (25%), nitric acid (70%), pure water, Dowex Monosphere 550A anion exchange resin (OH form, 590 ± 50 µm), and Dowex AG1-X8 anion exchange resin (Cl form, 100–200 mesh) were obtained from FUJIFILM Wako Chemicals (Tokyo, Japan). These reagents were used as received or diluted with the appropriate volume of pure water, as needed. Chelex-100 (Na form, 100–200 mesh) was purchased from Bio-Rad Laboratories (Tokyo, Japan). It was preconditioned as the ammonium form before use. Actinium-225 nitrate (37 MBq, 99.99% radionuclidic purity) was purchased from Oak Ridge National Laboratory and used as an authentic 225Ac source.
Methods
General
All the following procedures were performed in a ventilated glove box. Inside pressure of the glove box was set at negative 50 Pa, and no specific system for 222Rn handling was installed. A bag-in/out protocol with polyethylene bag (thickness 100 µm) was employed when transferring samples across the glove box to avoid releasing 222Rn and other possible radioactive materials into laboratory [Online Resource 1–3]. The maximum daily permission for handling 226Ra in our laboratory is 148 MBq (4 mCi).
Ra recovery from legacy needles
Radium needles (∅1.6 × 25 mm; 1–2 mCi-226Ra/needle) were sectioned into 5–6 pieces by an ordinal tube cutter (nipper type, for 1/16” stainless tubes). The pieces, which were collected in a 50-mL glass bottle with a polypropylene screw cap (Duran Wheaton Kimble, Germany), were mixed with 3 mL of a Chelex-100 resin slurry and 7 mL of pure water. The tightly capped bottle was sonicated daily for a period of one week to one month. Additional processes were not conducted.
Afterward, the Chelex-100 resin was filtered from those mixed materials by an empty cartridge (Bond Elut, 5 mL, Agilent Technologies, CA, USA), where the extracted 226Ra had been adsorbed on the resin. Then 1 M HCl (5 mL) and subsequent pure water (10 mL) for rinsing were loaded into the cartridge to elute 226Ra from Chelex-100. The eluant was loaded into an anion exchange resin (16 mL, Monosphere) to remove chlorides. Then the resin was washed with 10 mL pure water. The recovered solution was evaporated at 130°C under a vacuum, yielding dried 226Ra in the hydroxide form.
If the activity of the mixture of needle pieces and Chelex-100 residue was above a certain threshold, the mixture was returned to the bottle. To ensure the Chelex-100 function for adsorbing 226Ra effectively, a portion of conc. ammonium solution was added to adjust the pH of the slurry ≥ 10, and the same procedure was carried out repeatedly.
Target box design and target preparation
The 226Ra target is prepared by electrodeposition. Figure 1 shows the target box assembly. A Ti cylindrical cavity (#3 in Fig. 1) with a volume of about 3.5 mL was used for the reservoir for electroplating and the dissolving vessel for the Ra target after activation. A Pt rod (∅3 mm, anode for electroplating) was held by a polyimide-made screw with O-rings (#7). The bottom of the Ag cavity (#5) was assembled with both #3 and a polyimide electric insulator (#4). It should be noted that the Ra-depositing surface with a conical shape (#5) was fabricated with Au by hot isostatic pressing on the Ag body to ensure chemical resistance.
Purified dried 226Ra, which ranged from 400 to 1050 µCi (or µg on the weight scale), was dissolved in 1 mL of 0.1 M HCl and 2 mL of 0.5 M ammonium acetate to prepare the electrolyte. The electrolyte was placed in the target box, and a constant current of 100 mA DC was applied in the pulse mode (5 Hz, on in 0.1 s and off in 0.1 s) for 3 h with a 15-mm gap between the cathode and the anode. After the electrodeposition process, the electrolyte was removed from the cavity by pipette work, and introduced in and removed from 2 mL of pure water twice to wash out the residual electrolyte. These solutions, which may contain undeposited free 226Ra, were collected. Then the deposition efficiency was evaluated by measuring the 226Ra activity. The cavity stood undisturbed overnight (> 15 h) to dry the Ra surface naturally in a ventilated glove box. Eventually, the Pt anode was withdrawn from the cavity and sealed with a thin Nb foil (50 µm). The cavity at the beam entrance was sealed with a 50-µm-thick Nb foil (#2 in Fig. 1) with #1.
Activation
Activations were carried out by 34 MeV H2+ (ionized molecular hydrogen) provided by NIRS-AVF-930 cyclotron at a nominal intensity of 10 µA for 3–5 h. This condition increased the intensity of lower energy particles accelerated by a relatively larger cyclotron to give 17 MeV protons at nearly 20 µA by splitting of the kinetic H2+ ion at the vacuum isolation window. The estimated proton energy on the target material was 15.6 MeV by passing through the vacuum foil (Al, 100 µm), the He cooling layer (30 mm), and the target foil (Nb, 50 µm).
To enrich the expected 225Ac yield as much as possible, the proton energy was set slightly higher than the energy for the estimated highest cross-section of the 226Ra(p,2n)225Ac [9]. In the case where Ra increases, this activation condition is applicable directly, and a minimal difference is expected in the yield and radionuclidic purity of 225Ac.
Separation of 225Ac from the target matrix
Figure 2 shows our newly developed separation procedure, which was implemented 3–4 days after the end of bombardment (EOB). The eluent concentration was determined to be a thinner condition that does not affect the separation performance, considering ease of handling, reduction of corrosion risk to the equipment (automation to be performed in our future study), and to carry out the purification process repeated twice by the same procedure. The activated target was dissolved in 3 mL of 0.7 M HNO3, and the solution was loaded slowly into a DGA cartridge (N,N,N’,N’-tetra-n-octyldiglycolamide, 1 mL, Eichrom Technologies, IL, USA). To increase the recovery of leftover of Ac/Ra, another 3 mL of 0.7 M HNO3 was introduced into the target cavity twice and the respective rinsing fractions were also loaded into the same DGA cartridge.
The DGA cartridge was washed with 20 mL of 0.7 M HNO3 to remove residual 226Ra. Then 5 mM HNO3 (10 mL) was loaded into the DGA to elute 225Ac, which is the fraction collected in an intermediate reservoir. Subsequently, the crude 225Ac fraction was loaded into a LN cartridge (di(2-ethylhexyl)orthophosphoric acid, 2 mL, Eichrom Technologies), the cartridge was washed with 10 mL of 50 mM HNO3 to eliminate trace amounts of 226Ra, and then well purged. All the above waste fractions were collected as the Ra recovery fraction, which was recycled for the next use. Eventually, 225Ac was stripped by loading 0.7 M HNO3 (10 mL) and collected into another intermediate reservoir.
The actinium-225 solution in this separation step contained by-produced 226Ac (β 83%, EC 17%, α 6×10− 3%; T1/2 = 29.4 h), which was unavoidably generated via the 226Ra(p,n)-channel in our activation condition. To increase the radionuclidic purity of 225Ac, the intermediate product was allowed to cool for 2–3 weeks, which is equivalent to 10 half-lives or more for 226Ac. After the cooling, the above separation protocol was repeated as the secondary purification.
Although the twice purified 225Ac was free from or had negligible 226Ac contamination in 0.7 M HNO3 (10 mL), it was too acidic for further use. Thus, an anion exchange resin (AG1-X8, 100–200 mesh, Cl form) was employed to exchange the counter anion of 225Ac with chloride and remove HCl from the product by evaporation of the above sample (130°C under vacuum). The final product, which was in a chemical form of 225AcCl3, was reconstituted in a buffer and volume for further use.
Recycle mode for Ra
All fractions possibly containing 226Ra were collected into a single vessel. The solution was adjusted to a pH ≥ 10 by adding conc. ammonium solution and then loaded into a column filled with the Chelex-100 resin (0.5 mL, NH4 form) to concentrate 226Ra. After washing the column with 10 mL of pure water, 226Ra was stripped by passing 1 M HCl (5 mL), and the eluant was led to an anion exchange resin column directly (16 mL, Monosphere, OH form). The Ra fraction was desalted by the anion exchanger, and an additional 10 mL of pure water was loaded to wash out the residual 226Ra. The collected 226Ra with a volume of about 15 mL was subsequently evaporated at 130°C under a vacuum to yield purified 226Ra in the hydroxide form, which was ready for the next use as the electrolyte.