Cyclotron Production and Purification of ⁸³Sr as a ⁹⁰Sr Substitute for Positron Emission Tomography (PET)

Abstract

Radioactive contaminations in soil, which originate from nuclear power production, nuclear weapon testing, or uncontrolled release, are of great environmental concern. One of the major fission product contaminants is ⁹⁰Sr, whose high mobility demands a method to track contamination pathways and remediation processes. Positron emission tomography (PET) is a valuable tool for the required studies. As a β⁻/γ-emitter, ⁹⁰Sr is not suitable for PET, which requires β⁺-emitters. As an alternative, ⁸³Sr, with a 12% intensity of β⁺-emission and a half-life of 32.4 h, is an appropriate PET substitute for ⁹⁰Sr. We produced ⁸³Sr with an enriched target of [⁸⁵Rb]RbCl in a ⁸⁵Rb(p,3n)⁸³Sr reaction. The target material was bombarded with 36.22 MeV protons (ø 1.78 µA, 315 min), at a solid target station at the cyclotron U-120M (NPI CAS). The irradiated target (1.5 GBq) was dissolved in water, evaporated to dryness, redissolved in nitric acid, and transferred onto a Sr-selective cartridge (Sr-SpecTM, TRISKEM, France). Following target material wash out, ⁸³Sr elution with water, solvent evaporation, and reformulation (in dilute nitric acid) yielded 1.2 GBq (82% radiochemical extraction efficiency, non-decay-corrected) of an ⁸³Sr-solution. The easy and fast method is able to produce non-carrier-added ⁸³Sr with high radionuclidic purity.

1. Introduction

The radionuclide ⁹⁰Sr is a nuclear fission product, formed mainly in nuclear power plants. Almost all ⁹⁰Sr detected in the environment originates from one of three primary man-made sources. These are (i) the operation of nuclear power plants, (ii) the global atmospheric fall-out of nuclear weapon tests, and (iii) nuclear accidents like those at the Chernobyl and Fukushima Daiichi nuclear power plants [1,2]. Due to its chemical similarity to calcium, incorporation into plants and animals is a major concern for human health. Therefore, decontamination of ⁹⁰Sr-containing soils is of high relevance. An emerging approach is plant-based remediation/phytoremediation. Root exudates are supposed to extract the ⁹⁰Sr, which will be transported into the plant matrix, where it can later be collected and separately disposed of [3,4].

The ⁹⁰Sr itself has a half-life of 28.9 a [5]. For a three-dimensional understanding of the remediation behavior of ⁹⁰Sr by plants, positron emission tomography (PET) is a promising technique. The decay mode of ⁹⁰Sr itself is the only drawback; as a pure β⁻-emitter, PET imaging with this isotope is not suitable. Checking the other isotopes of strontium from ⁸⁰Sr to ⁹⁰Sr, stated in

Table 1. Overview of the strontium isotopes, with the corresponding half-lives and their main decay modes (EC, electron capture; nuclear data [5,6,7,8,9,10,11,12,13,14,15]).

Isotope	Half-Life t1/2	Decay Modes (β+-Intensity)
80Sr	106.3 min	EC, β+ (9.2%)
81Sr	22.3 min	EC, β+ (29%)
82Sr	25.3 d	EC
83Sr	32.4 h	EC, β+ (12%)
84Sr	stable	–
85Sr	64.8 d	EC
86Sr	stable	–
87Sr	stable	–
88Sr	stable	–
89Sr	50.6 d	β−
90Sr	28.9 a	β−

, shows different options, with ⁸⁰Sr, ⁸¹Sr, and ⁸³Sr as partial β⁺-emitters with half-lives ranging from 22.3 min (⁸¹Sr) up to 32.4 h for ⁸³Sr [5,6,7,8,9,10,11,12,13,14,15]. For imaging soil distribution and plant uptake, the half-life of ⁸³Sr with 32.4 h provides an optimal time scale for our PET experiments for root exudate-based mobilization of strontium in soil. The β⁺-emission has an intensity of 12%, which is sufficient for PET imaging. Both β⁺-emission and electron capture (88%) result in the daughter nuclide ⁸³Rb (t_1/2 = 86.2 d), which in turn decays to stable ⁸³Kr [9].

One route for the production of ⁸³Sr could be the use of heavy ion bombardment via ⁶⁵Cu(²²Ne,5n)⁸²Y → ⁸³Sr or ⁷⁵As(¹²C,4n)⁸³Y → ⁸³Sr reactions, as described by Broda et al. [16], as well as with the ⁸²Kr(³He,2n)⁸³Sr reaction, as described by Blessing et al. [17]. The availability of heavy ion beams and the separation of the ⁸³Sr from the target and the matrix material have not been described. Instead, Kastleiner et al. [18] described the production via a nuclear proton reaction with a cyclotron. They used an [⁸⁵Rb]RbCl isotopically enriched (99.4%) target irradiated by a proton beam. The determined cross-sections of the ⁸⁵Rb(p,3n)⁸³Sr reaction are shown in Figure 1. The optimal energy range for the preferred nuclear reaction can be achieved with proton energies of 30–40 MeV, in order to minimize the formation of unwanted side products as ^85gSr (t_1/2 = 64.8 d) and ^85mSr (t_1/2 = 67.6 min) [11,18,19]. In consideration of the cyclotron Cyclone 18/9 (IBA, Louvain-la-Neuve, Belgium) available at the research site in Leipzig, which offers a maximum proton beam energy of ≤18 MeV, the favorable nuclear reaction is not feasible. In addition, the TR-FLEX cyclotron (ACSI, Richmond, BC, Canada) at the research site in Dresden-Rossendorf offers a ≤30 MeV proton beam [20]. Due to its low proton energy range, an efficient production of ⁸³Sr is not possible at our HZDR infrastructure. The Nuclear Physics Institute of the Czech Academy of Sciences in (Řež, Czech Republic) is offering proton energies up to 37 MeV with the U-120M cyclotron. This energy range is ideal for the production of ⁸³Sr (see Figure 1) and minimizes the formation of ^85g/mSr.

With the high energy proton beam of the U-120M cyclotron, we want to produce ⁸³Sr with an enriched target of [⁸⁵Rb]RbCl in an ⁸⁵Rb(p,3n)⁸³Sr reaction. The procedure for separation of the radiotracer from the target material and the recovery of it are adapted to the procedure of Mansel et al. [25]. The prepared ⁸³Sr was used for further PET experiments [26].

2. Materials and Methods

2.1. General

2.1.1. Target Disks

The target disks for the targets consist, in general, of an aluminum disk 20 mm in diameter and 2.5 mm thick, with a centered recess of 8 mm in diameter and depth of 1.5 mm (see Figure 2a). As cover, an aluminum foil 20 mm in diameter and 50 µm thick is used. For the final target disk (aluminum), a narrow channel, 1.1 mm deep, 1.5 mm thick, and 0.5 mm away from the edge of the target disk, was inserted. This allows for the placement of a rubber seal. For more details, see Figure 2b.

2.1.2. Ion Chromatography

An ion chromatography (IC) system, consisting of two ICS-1600 pump compartments with a column heater, suppressor system (CSRS 300, 4 mm, Dionex, Sunnyvale, CA, USA), and conductivity detector (DS6 heated conductivity cell, Dionex, Sunnyvale, CA, USA), in cat- and anion mode was used. For sample injection, an autosampler system Dionex PMC ICSP AS (ThermoFisher Scientific, Waltham, MA, USA) was used. All samples were injected onto the IC system with a volume of 25 µL.

For anion detection, an isocratic method with a mixture of a 4.5 mM aqueous sodium carbonate buffer and a 1.4 mM aqueous sodium hydrogen carbonate buffer was used, with a flow rate of 1.2 mL/min. The column system consists of a guard column IonPac AG22 (4 × 50 mm, Dionex, Sunnyvale, CA, USA) and an analytical column IonPac AS22 (4 × 250 mm, Dionex, Sunnyvale, CA, USA). The columns were equilibrated at 30 °C in the column oven system. The suppressor was operated at a current of 35 mA. The retention times were 4.22–4.29 min for chloride and 6.42–6.47 min for nitrate. The total method runtime was 14 min.

For cation detection, an isocratic method with an aqueous 18 mM methanesulfonic acid (MSA) buffer was used, with a flow rate of 1.0 mL/min. The column system consists of a guard column IonPac CG 12A (4 × 50 mm, Dionex, Sunnyvale, CA, USA) and an analytical column IonPac CS 12A (4 × 250 mm, Dionex, Sunnyvale, CA, USA). The columns were equilibrated at 30 °C in the column oven system. The suppressor was operated at a current of 60 mA. Retention times were 7.51–7.81 min for rubidium and 16.33–17.00 min for strontium. The total method runtime was 25 min.

Data evaluation was carried out with the chromatography software Chromeleon 7.2.10 (Thermo Fisher Scientific Inc., Waltham, MA, USA).

2.1.3. Activity Determination and γ-Spectrometry

Activity determinations for radiochemical procedures and sample preparation were performed using either an ISOMED 2010 dose calibrator (NuviaTech Healthcare, Rueil-Malmaison, France) or γ-spectrometry. For γ-spectrometry measurements, a GEM40P4-76 high-purity germanium (HPGe) detector equipped with a DSPEC 502 signal processing module (both ORTEC AMETEK, Oak Ridge, TN, USA) was utilized. The liquid nitrogen-cooled detector was oriented vertically within a lead-shielded chamber. Samples were positioned at distances of either 100 mm or 410 mm from the detector, depending on their radionuclide content. This configuration maintained measurement dead times between 1.1% and 14.8%. Measurement durations were set to either 2 h or 1 d. Energy and efficiency calibrations were performed using the NG3-234 geometry reference standard (Eckert & Ziegler, Berlin, Germany), which consists of a 14-nuclide mixture in a 1 mL volume with a density of 1 g/cm³. Spectra were recorded and analyzed using GammaVision software, version 8.00.03 (ORTEC AMETEK, Oak Ridge, TN, USA).

2.1.4. Chemicals and Materials

All chemicals used were suprapure grade. Deionized water (DI water) was supplied by a Milli-Q^® IQ 7005 (Merck Millipore, Burlington, MS, USA) ultrapure water purification system.

The term “evaporated under reduced pressure” describes the removal of solvents under reduced pressure; a gentle stream of argon and elevated temperatures (115–130 °C) were applied too. All acid fumes formed during evaporation processes were trapped with an acid-air-washing system (0.1 M aqueous NaOH solution) to prevent them from entering the vacuum pump.

The Sr-SpecTM resin cartridge (SR RESIN FSRS180830; length 3 cm, diameter 1 cm) from TRISKEM Int. (Bruz, France) was pre-equilibrated with 30 mL of DI water and 30 mL of 8 M HNO₃.

2.1.5. Irradiation Facility—Isochronous Cyclotron U-120M

The isochronous cyclotron U-120M was originally designed and manufactured at JINR Dubna as an accelerator for light positive ions (H⁺, D⁺, ³He²⁺, ⁴He²⁺), providing maximum energies of several tens of MeV (K = 40). The facility was commissioned in 1977 and has since been continuously operated and systematically upgraded. A major upgrade involved the conversion of the cyclotron to negative-ion (H⁻, D⁻) operation, enabling extraction of (H⁺, D⁺) beams using the stripping technique. This upgrade, completed between 1996 and 1998, resulted in an approximately one-order-of-magnitude increase in the extracted (H⁺, D⁺) beam currents. Currently, the cyclotron can deliver an external proton beam with a maximum energy of 36–37 MeV and a maximum beam current of approximately 30 µA.

2.2. Preparation of the RbCl Targets

The targets were prepared by pressing powdered ^natRbCl (FLUKA, Seelze, Germany) or [⁸⁵Rb]RbCl (enrichment 99.5% ⁸⁵Rb, STB Isotope Germany GmbH, Hamburg, Germany) into a target backing using a dedicated pressing tool. The backing had the shape of a disk with a diameter of 20 mm. The RbCl powder was compacted into a cavity with a diameter of 8 mm located at the center of the backing. The RbCl powder was pressed at pressures of 5.9 MPa or 9.8 MPa, resulting in a mechanically stable RbCl pellet. The pressing pressure was chosen experimentally to ensure that the prepared layer was sufficiently compact while avoiding undesirable extensive extrusion of parts of the periphery layer from the cavity and preventing mechanical deformation of the backing during pressing. The thickness of the RbCl layer and of the thickness of the backing was selected such that the beam energy loss in the layer was optimal and the major part of the beam was fully stopped in the cooling water.

Since the behavior of the RbCl layer under irradiation was not known in advance, several test irradiations were performed using targets with layers of commercially available and inexpensive ^natRbCl with various beam currents. Two types of targets were used:

Test targets (dimensions shown in Figure 2a) were used to determine beam parameters, in particular the proton current and thus the thermal power deposited in the layer and in the target itself. For one of the test irradiations, a ^natRbCl target with a mass of 172.9 mg was prepared. The target was pressed at a pressure of 9.81 MPa (see Figure 3a,b).

One enriched target (dimensions shown in Figure 2b) was supplemented with an Al foil of a thickness of 55 µm placed in front of the [⁸⁵Rb]RbCl layer to prevent possible dispersion of the irradiated material into the target holder or to the ion-beam line. The Al foil was perforated with several small holes to allow for the release of gases, which is generated mainly at the beginning of irradiation. For ⁸³Sr production, the target disk was filled with 171.9 mg of isotopically enriched [⁸⁵Rb]RbCl (enrichment 99.5%), pressed with 1000 kg (see Figure 3d), and then irradiated.

2.3. Cyclotron Production of ⁸³Sr

The target disk with pressed RbCl powder was placed into a target holder (see Figure 4a,b), which was installed directly on the cyclotron ion-beam line. The front, irradiated target site is in a vacuum, while the back site is cooled with water. In Figure 4c, a schematic overview of the target holder is shown. The proton beam was extracted from the cyclotron to the ion-beam line, focused or defocused by the quadrupoles and collimated into a shape that corresponds to the size of the target. The aluminum collimator is positioned in front of the target layer to ensure that only the area with target material is irradiated. The target was irradiated for 315 min with protons with a proton energy of 36.39 MeV and an average current of 1.78 µA (total charge: 33,660 µC).

2.4. Purification of ⁸³Sr

The bombarded target material (1.5 GBq, end-of-bombardment [EOB]) was dissolved in 1.5 mL of DI water, and the target holder was rinsed with 1.25 mL of DI water. The water fractions were combined and collected in a v-vial for evaporation under reduced pressure. The solid residue was redissolved in 1 mL of 8 M HNO₃ and administered to the Sr-SpecTM resin cartridge. The setup consisted of a polytetrafluoroethylene (PTFE) tubing system which was connected to the Sr-selective cartridge via a three-way valve, and via another PTFE tubing to a syringe pump equipped with two syringes, filled with water and 8 M of HNO₃, respectively. Both syringes were connected to non-return valves to prevent mixing of the different eluents (Figure 5), and they could be controlled individually via the syringe pump. The v-vial was washed with another 1 mL of 8 M HNO₃, which was also transferred onto the cartridge. Both volumes were collected as fraction 1. Further, 2 mL of 8 M HNO₃ aliquots was added onto the cartridge and eluted in fractions 2–6 (syringe pump, speed 0.25 mL/min). Switching to DI water, the 2 mL of fractions (syringe pump, speed 0.25 mL/min) 7–13 was collected. Fractions 9–11 contained the ⁸³Sr-activity and were combined. The aqueous solvent was removed under reduced pressure. The dried residue was redissolved in 1 mL of 1 mM HNO₃. This resulted in a final solution containing 1.2 GBq ⁸³Sr (radiochemical extraction efficiency [RCEE] = 82% non-decay-corrected [ndc]), with a total extraction time of 194 min (start of the dissolution of the target material). The radionuclidic purity (RNP) was determined via γ-spectrometry as >99%.

2.5. Target Material Recovery

2.5.1. Non-Radioactive Test with ^natRbNO₃

In a glass v-vial, 257 mg of ^natRbNO₃ was dissolved in a mixture of 1 mL of conc. HCl and 100 µL of DI water. The liquid was evaporated under reduced pressure. The dry residue was dissolved in 1 mL of DI water, and a 10 µL sample was taken for ion chromatography analysis (10 µL sample diluted in 4.99 mL of DI water). To the dissolved salt, 1 mL of conc. HCl was added, and the solvent was evaporated under reduced pressure. The procedure of redissolving in DI water, sampling, addition of conc. hydrochloric acid, and evaporation was repeated seven times, to result in an off-white crystalline solid after eight repetitions. The IC analysis shows >99% of chloride content in the last samples.

2.5.2. Recovery of ⁸⁵Rb Target Material

To recover isotopically enriched target material, fractions 1–3 from Sr-cartridge elution were combined, and the nitric acid was evaporated under reduced pressure until dryness was reached. The off-white solid was redissolved in 2 mL of conc. HCl, followed by the evaporation of it under reduced pressure. This process was repeated seven times to result in 165.4 mg of a colorless solid (total recovery = (165.4 mg/171.9 mg) · 100% = 96%). IC analysis of a sample shows >99% of chloride content.

2.6. Positron Emission Tomography—Phantom

The feasibility of ⁸³Sr for positron emission tomography in materials science was quantified by utilizing a phantom. To mimic the attenuation properties of sands and soils, which are a major target for ⁸³Sr PET experiments, a material with similar attenuation coefficients for the 511 keV annihilation radiation is required. From all readily available polymers, the mass attenuation coefficient for PTFE (0.179 1/cm, [27]) is the closest to that of silicate sand (0.229 1/cm at 20% porosity, [27]). The phantom is made up of a PTFE cylinder (50 mm diameter, 50 mm height), with blind holes of 1–5 mm diameter drilled to a depth of 30 mm.

An ⁸³Sr-solution of 22.0 MBq/mL was injected into all holes. The phantom filled with a total activity of 16.5 MBq was inserted into a preclinical PET scanner (ClearPET/Elysia-Raytest, Straubenhardt, Germany; Sempere Roldan et al. [28]), which provides a voxel size of 1.15 × 1.15 × 1.15 mm³. Data acquisition was performed for 20 min. The tomograms were reconstructed using the OSMAP One-Step-Late reconstruction algorithm of the STIR library [29]. Corrections for decay, photon scattering, and random coincidence events were applied as described by Schöngart et al. [26]. To prevent artifacts due to different fill height of the bore holes, the resulting datasets were masked. Only the bottom voxel layer (1.15 mm) of the tracer-filled bore holes is used for analysis.

3. Results and Discussion

For the first test of the target setup, a natural RbCl target is prepared by pressing ^natRbCl powder into an aluminum holder, as shown in Figure 3a,b. The irradiation was performed for 10 min with 36.22 MeV protons at 5 µA current, resulting in a dark blue ^natRbCl target pellet. No signs of melting or sublimation of the target material are observed, as shown in Figure 3c.

With a modified target disk (shown in Figure 2b), the enriched target material of [⁸⁵Rb]RbCl was prepared in a similar manner to the previously described test target. The enriched [⁸⁵Rb]RbCl target was irradiated with protons on the ion-optical beam line of the cyclotron at a maximum achievable energy of approximately 37 MeV and an average beam current of 1.78 µA.

The power losses in the individual layers were as follows: Al foil: −0.34 W, [⁸⁵Rb]RbCl layer: −7.14 W, Al backing with a thickness of 1 mm: −7.54 W, and beam stopping in water: −57.76 W [30]. The irradiation time was 315 min, corresponding to a total collected charge of 33 660 µC. A schematic overview of the target assembly with the relevant beam parameters is shown in Figure 6.

After irradiation, the target was left in the target holder for 12 h to allow for the decay of short-lived radionuclides, before it was packed and shipped to the research site in Leipzig, Germany.

After the bombardment, a melting effect of the bulk target material was visible to some extent, seen as colorless spots in Figure 3e. In addition, sublimation of target material took place, which was clearly visible as target residue on the target cover, as shown in Figure 3f.

For the separation and purification of the produced ⁸³Sr, the method described by Mansel et al. [25] was adapted. The procedure was first tested with non-radioactive (natural) rubidium/strontium mixtures. The preliminary separation experiment showed good separation for both elements.

The adapted method was also used for the irradiated target material. After bombardment and transport, the activity was determined with γ-spectrometry to be 1.5 GBq of ⁸³Sr (Figure 7a). Besides the main product, some radiometal impurities could be detected in the γ-spectra, as shown in Figure 7a. These impurities were determined as ⁸³Rb, ⁸⁴Rb, and ⁸⁵Sr. The dissolution of the target material was easy to perform, due to the excellent water solubility of RbCl and SrCl₂. The water was evaporated, and the residue redissolved in nitric acid (8 M), which was necessary for the separation on the Sr-selective cartridge. Compared to strontium, rubidium has a high retention under these strong acidic conditions. Horwitz et al. [31] showed the high affinity of strontium towards the resin with a determined capacity factor k’ of ~90 compared to all other alkali metals, with k’ < 10. The rubidium was eluted in the first fractions. After washing of the cartridge, the elution of the ⁸³Sr was performed by changing the eluent from nitric acid to water. The ⁸³Sr was contained in fractions 9–11 (see Figure 8a), which were combined. The ⁸³Sr fractions were evaporated to dryness, and the residue was then redissolved in diluted nitric acid. The resulting solution contained a final activity of 1.2 GBq (RCEE of 82%) of [⁸³Sr]Sr(NO₃)₂. The ⁸³Sr-solution was then used for various PET experiments [26].

The complete separation was performed in 194 min, where the solvent evaporations were the most time-consuming steps. In future purifications, the aqueous target solution should only be diluted with conc. nitric acid, to avoid one of the two evaporation steps.

An aliquot of the ⁸³Sr-solution analyzed via γ-spectrometry showed an RNP > 99% ⁸³Sr and minor impurities of ⁸⁵Sr (see Figure 7b). After decay of the ⁸³Sr (ca. 330 d), an additional γ-spectrum (Figure 7c) was recorded in order to resolve spectral signals which were hidden by strong ⁸³Sr-signals. Only very minor impurities of ⁸³Rb and ⁸⁵Sr, less then <1% decay corrected to the total activity of the ⁸³Sr at the end of synthesis, are detected. These impurities are the results of either the incomplete separation during the purification, or, especially in the case of ⁸³Rb, being formed by ⁸³Sr as a decay product.

Furthermore, the enriched target material was recovered from the cartridge fractions and transformed into the chloride-form. To determine the efficiency of the nitrate–chloride exchange process, a sample of ^natRbNO₃ was used in the first approach. The solid residue was dissolved in conc. hydrochloric acid and then evaporated under reduced pressure. This process was repeated with the residues for a total of eight cycles. After every evaporation step, a sample was taken to determine the chloride–nitrate ratio with ion chromatography. These experimental results are shown in Figure 8b and suggested a minimum of six evaporation steps, to ensure the absence of nitrate in the rubidium salt. For the recovery of the enriched target material, seven evaporation steps with conc. hydrochloric acid were performed. The [⁸⁵Rb]RbCl was obtained as a colorless powder with 96% (165.4 mg) recovery (see Figure 3g). Ion chromatography showed an >99% content of rubidium chloride. Via γ-spectrometry, <1% (from total activity) of impurities were detected in the recovered [⁸⁵Rb]RbCl. The main radioactive impurity was ⁸⁴Rb (881.5 keV [10]) (see Figure 7d).

To assess the achievable resolution in PET, a PTFE phantom was used. The measured activity distribution in the tomogram is shown in Figure 9a as a projection along the length of the ⁸³Sr-filled holes. The PET acquisition yielded 2.4 × 10⁶ total counts, of which 1.8 × 10⁶ were so-called “true events” and contributed to the reconstruction of the tomogram [26]. Figure 9b shows line profiles across the ⁸³Sr-filled holes. To estimate the spatial resolution achievable with ⁸³Sr, the line profiles were fitted a gaussian functions. The results are presented in Figure 9c. For 99.7% confidence intervals, all bore holes showed a one-sided peak broadening between 2.38 mm and 2.66 mm with respect to the bore radius.

4. Conclusions

In an international collaboration between the German Helmholtz-Zentrum Dresden-Rossendorf research site in Leipzig and the Czech Institute of Nuclear Physics CAS, a fast and high-purity method was established to produce non-carrier-added ⁸³Sr. With the isotopically enriched [⁸⁵Rb]RbCl target, we successfully produced ⁸³Sr in a ⁸⁵Rb(p,3n)⁸³Sr reaction. The target material and ⁸³Sr were separated utilizing a Sr-selective resin, and formulated as [⁸³Sr]Sr(NO₃)₂ solution with an 82% radiochemical extraction efficiency and with >99% radionuclidic purity. The produced ⁸³Sr was used in PET experiments, serving as a ⁹⁰Sr analog to quantify both phytomobilization and abiotic remediation of contaminated soils.