Research ArticleBasic Science Investigation

Optimized Methods for the Production of High-Purity 203Pb Using Electroplated Thallium Targets

Shefali Saini, Jennifer L. Bartels, Jean-Pierre K. Appiah, Jason H. Rider, Nicholas Baumhover, Michael K. Schultz and Suzanne E. Lapi
Journal of Nuclear Medicine November 2023, 64 (11) 1791-1797; DOI: https://doi.org/10.2967/jnumed.123.265976

Abstract

203Pb is a surrogate imaging match for 212Pb. This elementally matched pair is emerging as a suitable pair for imaging and targeted radionuclide therapy in cancer care. Because of the half-life (51.9 h) and low-energy γ-rays emitted, 203Pb is suitable for the development of diagnostic radiopharmaceuticals. The aim of this work was to optimize the production and separation of high-specific-activity 203Pb using electroplated thallium targets. We further investigated the radiochemistry optimization using a suitable chelator, tetraazacyclododecane-1,4,7-triacetic acid (DO3A), and targeting vector, VMT-α-NET (lead-specific chelator conjugated to tyr3-octreotide via a polyethylene glycol linker). Methods: Targets were prepared by electroplating of natural or enriched (205Tl) thallium metal. Scanning electron microscopy was performed to determine the structure and elemental composition of electroplated targets. Targets were irradiated with 24-MeV protons with varying current and beam time to investigate target durability. 203Pb was purified from the thallium target material using an extraction resin (lead resin) column followed by a second column using a weak cation-exchange resin to elute the lead isotope as [203Pb]PbCl2. Inductively coupled plasma mass spectrometry studies were used to further characterize the separation for trace metal contaminants. Radiolabeling efficiency was also investigated for DO3A chelator and VMT-α-NET (a peptide-based targeting conjugate). Results: Electroplated targets were prepared at a high plating density of 76–114 mg/cm2 using a plating time of 5 h. A reproducible separation method was established with a final elution in HCl (400 μL, 1 M) suitable for radiolabeling. Greater than 90% recovery yields were achieved, with an average specific activity of 37.7 ± 5.4 GBq/μmol (1.1 ± 0.1 Ci/μmol). Conclusion: An efficient electroplating method was developed to prepare thallium targets suitable for cyclotron irradiation. A simple and fast separation method was developed for routine 203Pb production with high recovery yields and purity.

Radiopharmaceuticals can be used for diagnostic or therapeutic applications based on the incorporated radionuclide. The term theranostic is a portmanteau word for therapy and diagnostic. In theranostics, an imaging surrogate is used to guide delivery of a personalized dosage for a disease condition (1,2). In nuclear medicine, theranostic radiopharmaceuticals use a common precursor to diagnose and treat the disease condition using radionuclides with similar or identical chemistry but decay properties that are suitable for imaging and therapy (3). In this context, 203Pb and 212Pb represent an elementally identical radioisotope pair that is particularly well suited for the development of theranostics.

Food and Drug Administration approved agents such as NETSPOT ([68Ga]Ga-DOTATATE; Advanced Accelerator Applications) and LUTATHERA ([177Lu]Lu-DOTATATE; Novartis) are routinely used in clinical settings for the diagnosis and therapy of somatostatin receptor positive neuroendocrine tumors (4,5). However, despite the potential of these theranostic agents, different radionuclides for imaging and therapy may often require different methods for chemistry optimization and different chelators. In addition, the in vivo biodistribution profiles of these radiopharmaceuticals labeled with 68Ga or 177Lu may be different (6,7). Therefore, to better match the diagnostic and therapeutic counterparts, elementally matched isotope pairs are highly desired. Elementally matched radiopharmaceuticals use the same radioactive element with isotopes that have decay properties making them suitable for diagnostic imaging (β+/γ-emitting) and therapeutic (α/β− emitting) applications. In this way, the in vivo biodistribution is identical and the imaging surrogate can be used to understand and predict the pharmacokinetics of the therapeutic. In addition, the use of an elementally matched isotope pair for theranostics adds confidence to dosimetry, thereby providing potentially more accurate treatment planning. Table 1 provides a list of elementally matched isotopes for theranostic matched pairs.

View this table:
TABLE 1.

Characteristic Properties of Elementally Matched Theranostic Isotope Pairs

203Pb and 212Pb are an emerging, elementally matched pair of high interest. 203Pb decays to stable 203Tl by electron capture with the emission of a low-energy γ-photon (279 keV, 81%) and no radioactive daughter, making it suitable for SPECT imaging applications (8). 212Pb is a daughter of 224Ra and decays by emitting 2 β− and one α particle, making it suitable for therapeutic applications (9–11). 212Pb is typically available from a 224Ra/212Pb generator, but commercial-scale manufacturing is feasible because of relatively straightforward chemistry for purification.

The present study investigated the production of 203Pb via proton irradiation of thallium targets (205Tl(p,3n) 203Pb) and development of a robust separation method to obtain a final product of high specific activity. A simple 2-column separation method was developed that requires small elution volumes with a separation time of less than 2 h. The final product was eluted in HCl (400 μL, 1 M), making it feasible for radiolabeling and shipping to other facilities. Further evaluation for radiolabeling was performed with a DO3A chelator to develop a standard operating procedure for apparent molar activity (AMA) analysis. Elemental analysis was determined using inductively coupled plasma mass spectrometry (ICP-MS) to analyze the impurities in the final product.

MATERIALS AND METHODS

All reagents were purchased from Sigma Aldrich unless otherwise noted. Additional details are provided in the supplemental materials (supplemental materials are available at http://jnm.snmjournals.org).

Thallium Target Preparation by Electroplating

An electroplating bath was prepared following the procedure from Suparman with some modifications (12). Briefly, the electroplating bath was prepared by mixing 250 mg of [natTl]Tl2O3 or [205Tl]Tl2O3, hydrazine hydrate (300 μL), NaOH (1 g), and ethylenediaminetetraacetic acid (1.5 g) in 10 mL of water. Copper (1.5-mm thickness) or gold (1-mm thickness) backings of 25-mm diameter were used as the cathodes. An electroplating station (Fig. 1) was designed and manufactured to help optimize uniform target mass deposition on a copper or gold coin. The details of the procedure are provided in the supplemental materials.

FIGURE 1.
FIGURE 1.

(A and B) Electroplating setup used for target preparation. (C–F) Copper and gold backings before (C and D) and after (E and F) electroplating.

Target Irradiation and Purification of 203Pb

All target irradiations were performed on an Advanced Cyclotron Systems TR24 cyclotron. Using an Advanced Cyclotron Systems 90° solid target holder (13), electroplated target disks of 205Tl were manually loaded in the target holder and irradiated at 24 MeV with varying currents from 5 to 40 μA and durations of 15 min to 3 h. The optimal beam profile and transmission were determined through maximization of the ion source injection system and the beamline vertical and horizontal focusing quadrupole magnet system settings on the cyclotron. With an effective beam energy of 24 MeV, the best transmission ratio was 93% with a 10%–15% beam spill on target collimators (top/bottom and left/right). A higher beam spill was chosen to help with cooling, provide better beam spread, and avoid a pinpoint beam spot that leads to target failure. With a pneumatic release system, irradiated target disks were loaded into lead containers and transferred for further processing. Targets were left overnight to allow for decay of short-lived isotopes, including 201Pb (half-life, 9.3 h) and 204mPb (half-life, 67.2 min).

For separation of 203Pb from the thallium target material, irradiated targets were dissolved in HNO3 (5–7 mL, 2 M) with gentle heating to 90°C. The dissolved target was loaded onto a solid-phase extraction column (1 mL) containing an extraction resin (lead resin; Eichrom) (50 mg), which was preconditioned with water (10 mL) and HNO3 (10 mL, 2 M). The solution was pushed through the column at 0.5–0.8 mL/min using a syringe or peristaltic pump. The resin was washed with additional HNO3 (10 mL, 2 M) to allow maximum removal of thallium target material from the resin bed. 203Pb was eluted using sodium acetate (5 mL,1 M, pH 5.5). This elution was loaded onto a second column containing 50 mg of weak cation-exchange resin previously preconditioned with water (5 mL) and NaOAc (5 mL, 1 M, pH 5.5). The resin was washed with HCl (1 mL, 0.01 M), and 203Pb was eluted as [203Pb]PbCl2 using HCl (400 μL,1 M). The fractions were analyzed with γ-ray spectroscopy. The separation scheme is shown in Figure 2.

FIGURE 2.
FIGURE 2.

Separation scheme of 203Pb purification from thallium target material. MQ = Milli-Q (Millipore Sigma).

ICP-MS

To investigate the trace metal impurities, ICP-MS analysis (Agilent 7700x) was performed for common contaminants including thallium, iron, copper, zinc, and stable lead in the final elution. Details of sample preparation are provided in the supplemental materials.

AMA Evaluation

AMA (GBq/μmol) was calculated by titration of [203Pb]PbCl2 with DO3A chelator (Supplemental Fig. 1B). The ratio of radiolabeling yield (%) versus concentration of chelator (log[DO3A] [μmol]) was plotted using GraphPad Prism for the half-maximal effective concentration calculation. Results are reported as GBq (Ci)/μmol. Complexation was analyzed using instant thin-layer chromatography silica gel (iTLC-SG) using 50 mM ethylenediaminetetraacetic acid as the mobile phase.

Radiolabeling

The VMT-α-NET targeting conjugate (Supplemental Fig. 1B) was used for radiolabeling studies (14). Stocks were prepared in NH4OAc (0.5 M, pH 5). Radiolabeling was performed using mass amounts from 100 to 0.5 μg of the desired compound. Reactions were incubated for 20 min at 70°C. Instant thin-layer chromatography silica gel plates were used to confirm complexation using 50 mM ethylenediaminetetraacetic acid as the mobile phase. Results were analyzed using GraphPad Prism and reported as MBq (mCi)/mmol.

RESULTS

Electroplated Thallium Target Preparation

To produce 203Pb, thallium metal (natTl/205Tl) was used to prepare targets. Extreme toxicity, low melting point, and nonavailability of thallium metal foils led us to explore an electroplating approach to target preparation (15,16). Electroplating conditions were optimized for electroplating periods extending from 1 to 5 h and solution pH ranging from 8 to 13. An approximately 14.5 ± 4 mg/h plating rate with a plating density of 76–114 mg/cm2 was achieved on a regular basis (n = 16), and a pH of more than 12.5 was found to be most suitable for rapid deposition of thallium metal. The electroplating bath could be reused several times (∼7–8 reactions) with regular replenishing of target material, which eliminated the need to recycle the target material after every plating cycle. However, further investigation is required to develop a methodology for recycling the starting thallium metal. A schematic of the electroplating setup used for the plating process is shown in Figure 1. Targets were prepared on copper and gold backings.

To analyze the relationship between target density and plating time, targets were plated for 1 and 5 h. Scanning electron microscopy was performed on the electroplated targets to determine the structure and elemental composition of the target prepared. For thallium targets prepared on copper backings, there were observable differences between the 1- and 5-h plating patterns in scanning electron microscopy analysis, indicating a nonuniform plating at 1 h whereas a uniform plating pattern was observed at the 5-h plating time point (Figs. 3A and 3B). However, gold backings showed uniform plating patterns at both the 1-h and the 5-h plating time points (Figs. 3D and 3E). Overall, 75% ± 5% of the thallium in the electroplating solution was deposited after 5 h. In addition, the percentage deposition of thallium in the final plating was found to be independent of plating time. Both gold and copper backings were observed to have approximately 89.3% ± 1.6% (by weight) thallium element deposited, with the remainder of the material composed of oxygen for both 1 h and 5 h as shown in the energy-dispersive x-ray analysis spectra in Figures 3C and 3F. Since thallium has a very high propensity to oxidize (15), a significant amount of oxygen (10.6% ± 1.6%) was also observed in scanning electron microscopy analysis. No other elemental peaks were found in the energy-dispersive x-ray analysis spectra. To achieve the production of the highest-purity 203Pb possible, we explored the use of a 99.1% enriched 205Tl target material, which contained trace levels of other contaminants such silver, zinc, boron, sodium, and silicon as described in the material’s certificate of analysis (Supplemental Table 1). The elemental analysis of the plated target material by scanning electron microscopy confirmed the presence of only thallium and oxygen, suggesting that high-purity 205Tl targets are achievable if electroplating is used.

FIGURE 3.
FIGURE 3.

Representative scanning electron microscopy images of copper (top) and gold (bottom) backing. (A and B) Analysis at 1 h after plating. (D and E) Five-hour time point for copper and gold backing, respectively. (C and F) Energy-dispersive x-ray analysis spectra for both gold and copper backing, respectively.

Target Irradiation and Purification of 203Pb

The complete separation scheme of 203Pb from thallium target material is as shown in Figure 4. We observed negligible (<2%) lead isotopes in the eluate and nitric acid wash, whereas the lead isotopes were eluted in NaOAc buffer (5 mL,1 M, pH 5.5) in the first column. During optimization of the separation procedures, we observed inconsistency in the chemical behavior of 203Pb when stored in NaOAc for a longer period, which was most likely due to its hydrolyzation at this pH. In addition, to achieve more than 95% elution of 203Pb, a large volume of NaOAc buffer (5–6 mL) was required. Therefore, concentration and purification of the elution from buffer to a more suitable labeling concentration was required. To address these challenges, a second column was used to further purify the 203Pb. Final elution of 203Pb separation from the enriched thallium target (205Tl) was achieved in a small fraction of HCl (∼400 μL, 1 M), with average recovery yields of 92.3% ± 3.5% (n = 3). At the end of processing, 4,477 ± 444 MBq (121 ± 12 mCi) 203Pb was obtained in the final elution (decay corrected to end of bombardment). The isotopic composition of the final elution product was found to be 203Pb (>99.5%) and 201Pb (<0.5%) as analyzed by γ-ray spectroscopy. The average production yields of 32.9 ± 6.3 MBq/μA-h (0.9 ± 0.2 mCi/μA-h) were achieved with a 98 ± 16 mg target.

FIGURE 4.
FIGURE 4.

Separation results for column 1 and column 2, with percentage recovery of 203Pb (n = 3, enriched target material 205Tl).

Our separation method required about 1 h from column loading to elution from the second column, with a very small final volume (<400 μL) and more than a 95% recovery yield.

ICP-MS

ICP-MS analysis was performed to further quantify the separation method and determine the presence of trace metal contamination. Results were compared for enriched 205Tl targets for copper and gold backings as shown in Table 2. The method developed indicated a good separation, with only a small amount of thallium (550 ± 950 ppb or 0.2 ± 0.4 μg) and lead (400 ± 150 ppb or 0.2 ± 0.1 μg) in the final 400 μL elution fraction. Significant SDs were observed in the reported results and are likely due to process variabilities in different batches.

View this table:
TABLE 2.

ICP-MS Results of Final 203Pb Elution to Determine Metal Contaminants

During optimization of the separation method for 203Pb, practical steps were taken to minimize the amount of residual trace metal contaminants in the product solution to improve the overall molar activity. For example, stable lead contamination is one of the primary concerns due to abundance of lead bricks in radiochemistry facilities. Therefore, the working station lead bricks were covered to reduce the amount of nonradioactive lead in the final elution and significantly reduced this contaminant. For copper backings, we found milligram amounts of copper in the dissolved target coming from dissolution of the backing in the HNO3, whereas switching to a gold target material alleviated this issue as indicated in Supplemental Table 2. The extraction resin is highly selective for lead isotopes in 2 M HNO3, which was confirmed during the separation because minimum breakthrough of lead (<2%) was observed in the flowthrough and the first wash of nitric acid as shown in Supplemental Table 3.

The molar activity of the final elution was also calculated using ICP-MS, and the average specific activity was about 5 TBq/μmol (4,745 ± 2,657 TBq/g) for an average batch size of 7.5 ± 1.4 GBq/mL (202.5 ± 38.7 mCi/mL).

AMA Evaluation

To determine the AMA, the DO3A chelator was used for titration analysis. Figure 5B represents the instant thin-layer chromatography graph for radiolabeled DO3A. AMA was calculated using the amount of radiolabeled versus free radioisotope. The average AMA (Fig. 6) was 37.7 ± 5.4 GBq/μmol (1.1 ± 0.1 Ci/μmol) (n = 3).

FIGURE 5.
FIGURE 5.

Instant thin-layer chromatography silica gel graph for unlabeled [203Pb]PbCl2 (A), [203Pb]Pb-DO3A (B), and [203Pb]Pb-VMT-NET (C).

FIGURE 6.
FIGURE 6.

Representative AMA measurement for [203Pb]Pb-DO3A (n = 3).

Radiolabeling Studies

Radiolabeling studies were optimized for the VMT-α-NET targeting conjugate, and a molar activity of 40.6 ± 11 GBq/μmol (1.1 ± 0.3 Ci/μmol) was achieved, indicating a high molar activity of 203Pb. A representative instant thin-layer chromatography silica gel graph illustrating the radiolabeled [203Pb]Pb-VMT-α-NET is shown in Figure 5C. It was important to understand whether the final product remained stable with similar radiolabeling yields over time. Thus, radiolabeling studies were performed for 2 consecutive days, and no changes in labeling efficiency were observed in the final product.

DISCUSSION

This work represents a method of production and separation of 203Pb using an enriched 205Tl reaction route and electrochemistry for target preparation. Thallium metal has a very low melting point, which was initially a concern during targetry optimization. Electroplating of targets from dissolved Tl2O3 was determined to be the preferred route. Targets were manufactured that could withstand irradiation times of up to 4 h and currents of 40 μA when irradiated with a 24-MeV incident beam energy without melting. In addition, the electroplated target enabled irradiation at 24-MeV proton incident energy without any degradation, which was not feasible with a powder target.

Irradiated targets resulted in suitable yields with a small amount of target material (<100 mg). However, the plated targets were peeling off when plating density exceeded 150 mg/mm2, and no consistent plating results were observed above this density. Therefore, for routine production, the plating density was kept below 150 mg/mm2.

The cross section for 203Pb production via the 205Tl(p,3n)203Pb reaction route is a maximum at 26 MeV (σ = 1,244 mb), indicating that a 30-MeV cyclotron could produce higher yields. However, a significant amount of the high cross section could be captured with a TR-24 cyclotron. With enriched thallium target material, production yields were significantly higher (32.9 ± 4.1 MBq/μA-h [0.9 ± 0.1 mCi/μA-h]) than previously published production routes for 203Tl(d,2n)203Pb (5.8 MBq/μA-h [0.2 mCi/μA-h]) (17) and 203Tl(p,n)203Pb (6.3 MBq/μA-h [0.2 mCi/μA-h]) (11). Theoretic production yields were calculated to be 38.1 MBq/μA-h (1.03 mCi/μA-h) for a 100-mg enriched target material with 24-MeV incident beam energy. The experimentally measured results (32.9 ± 4.1 MBq/μA-h [0.9 ± 0.1 mCi/μA-h] [n = 3]) were in close agreement with the theoretically predicted numbers for 24-MeV incident proton beam energy.

Isolation and purification of 203Pb from the postirradiation dissolved target using extraction resin chromatography were accomplished using a straightforward method that achieved high recovery yields after separation of more than 95% in the final elution. A small loading volume and controlled flow rate of 0.5 mL/min throughout the separation helped to minimize breakthrough of 203Pb in the loading and washing steps. A second column using weak cation-exchange resin was used to further concentrate and purify 203Pb from any residual Tl or trace metal contaminants and also enabled the final elution in a 400-μL volume. These methods have been tested with up to 3 GBq (80 mCi) of 203Pb, confirming the successful separation. Previous work by Garmestani et al. (17) established separation methods for 203Pb using the 203Tl(d,2n)203Pb reaction route. However, large elution volumes required additional drying steps resulting in production yields of 2.1 MBq/μA-h (0.1 mCi/μA-h) for natural and 7.5 MBq/μA-h (0.2 mCi/μA-h) for approximately 250-mg enriched 203Tl targets (17). Recent work by McNeil et al. (11) found a successful production method for 203Pb using natTl and 203Tl targets. Although the separation yield was reported to be 73.8% ± 2.1%, a significant amount of 203Pb was lost in the initial load (8.7 ± 0.3%) and wash (∼5%) steps (11). Recently, Nelson et al. (18) developed a production and separation method using 205Tl as a target material. Their separation method resulted in more than 83% recovery of 203Pb as [203Pb]PbCl2 in a 4-mL final volume in less than 4 h with production yields of 23.3 MBq/μA-h (0.6 mCi/μA-h) using a 250-mg powder target (18). Previous studies reported in the literature also worked with a high amount of starting material—between 250 mg and 4 g (11,18,19). Comparing our results with previous literature, we optimized an electroplating method to produce 203Pb for fast and consistent results with a small amount of starting material (∼100 mg).

Separation of 203Pb from enriched 205Tl using the extraction resin is very specific to lead, with minimum breakthrough in the initial load and wash (Supplemental Table 3 for complete separation). The target material was dissolved in HNO3 (5 mL, 2 M) at a temperature of 90°C and loaded on an extraction resin column. Overall, a very small amount of radioactive waste was generated while keeping the load and wash volumes small.

Gold coins were tested because of high amounts of measured copper (∼tens of milligrams) in the dissolved target solution when using copper backings. Such high amounts of copper could make it difficult to recycle the enriched target material in the future and introduce a possibility for contamination in the final 203Pb elution. In addition to cold contaminates, the copper backing produces γ-ray emitting zinc isotopes (such as 65Zn; half-life, 244 d), exposing personnel to potentially higher doses after bombardments. At the current bombardment angle, most of the 24-MeV incident energy is stopped on the copper backing, resulting in long-lived Zn radioisotopes emitting high-energy photons. Comparatively, gold is resistant to dissolution under harsh acid conditions with better heat conductivity. In addition, proton irradiation of gold backing produces mercury isotopes such as 197mHg (23.8 h [133 keV (intensity of γ-rays (Iγ), 33.5%), 279 keV (Iγ, 6%)]), 197gHg (64 h [77 keV (Iγ, 18.7%)]), 195mHg (41.6 h [261 keV (Iγ, 31%), 387.8 keV (Iγ, 2.18%), 560 keV (Iγ, 7.1%)]), and 195gHg (10.5 h [180 keV (Iγ, 1.9%), 207 keV (Iγ, 1.6%), 261 keV (Iγ, 1.6%), and 585 keV (Iγ, 2%)]). Although these radiocontaminants have a small cross section for energy below 20 MeV, these are relatively short-lived, implying that the gold backing could be reused after a significantly shorter decay time than for a copper backing (the contaminant with the longest half-life is 65Zn: 244 d [1.12 MeV (Iγ, 50%)]), making gold ideal as a backing material.

To compare the difference between electroplated thallium targets using gold and copper backings, high-purity germanium spectra (Supplemental Fig. 2) and ICP-MS analysis (Table 2) results were compared for the dissolved thallium target. ICP-MS analysis from previous studies by McNeil et al. (11) indicated 1.5 ± 0.7 μg of stable lead and 175 ± 105 μg of thallium in the final elution. Higher amounts of trace metal contaminants, specifically stable lead, can affect the molar activity of 203Pb. Our separation resulted in 0.2 ± 0.1 μg of stable lead in a 400-μL final volume, yielding a high molar activity of 4,745 ± 2,657 TBq/g (∼5 TBq/μmol) (n = 3). Previous reports of specific activity range include 52 TBq/g (32 GBq/μmol) by McNeil et al. (calculated on the basis of the data provided) (11), 405 ± 108 TBq/g by Li et al. (19), and 4,150 TBq/g (2.1 TBq/μmol) by Nelson et al. (18). Using ICP-MS, molar activity of 266.4 MBq/μmol (7.2 mCi/μmol) was reported by Máthé et al. (20) and 15 MBq/μmol (0.4 mCi/μmol) by Yao et al. (21), compared with a molar activity of about 5 TBq/μmol reported in the present study.

The molar activity numbers were not close to the theoretic specific activity of 1.1 × 105 TBq/g (3 × 106 Ci/g), but the numbers reported in this work are the highest yet reported to our knowledge. It is also worth mentioning that the molar activity calculations were performed for small batch sizes of about 3.7 GBq (∼100 mCi), and we anticipate improvement in these numbers as the batch size increases. AMA was also analyzed using a titration analysis with DO3A chelator, yielding a result of 37.7 ± 5.4 GBq/μmol (1.1 ± 0.1 Ci/μmol).

CONCLUSION

This project aimed to develop a robust target preparation method for production of high-specific-activity 203Pb via proton irradiation and an accompanying separation method to address the high demand for 203Pb as an imaging-compatible surrogate for the in vivo α-particle generator 212Pb. With a suitable half-life (51.8 h), large production batches could be shipped to a large geographic area to fulfill the needs for preclinical and clinical studies. We established a production method using enriched 205Tl and electroplated targets that can withstand beam currents of up to 40 μA. With a 3-h irradiation, an average production yield of 4.6 ± 0.43 GBq (126 ± 11.8 mCi) was obtained. The separation method for 203Pb was developed, and more than 95% overall separation yields were achieved in less than a 400-μL final volume, indicating a robust separation method. A standard operating procedure was also optimized for determining the AMA using DO3A chelator, and a high molar activity of about 37 GBq/μmol (1 Ci/μmol) was routinely achieved.

DISCLOSURE

This work was supported by the Department of Energy isotope program through grant DESC0020197 (principal investigator, Suzanne Lapi). This work was also supported in part by Viewpoint Molecular Targeting, now Perspective Therapeutics, of which Nicholas Baumhover and Michael Schultz are employees. No other potential conflict of interest relevant to this article was reported.

KEY POINTS

QUESTION: Is it feasible to produce significant amounts of 203Pb with high molar activity using enriched 205Tl target material?

PERTINENT FINDINGS: An electroplating method was developed to prepare target material (205Tl) that could withstand a 24-MeV incident beam and high current without using a degrader. A separation method was developed to achieve approximately 95% recovery yields of 203Pb with a processing time of less than 1.5 h. 203Pb production batches of 9.2 GBq/mL were achieved using a small amount of target material.

IMPLICATIONS FOR PATIENT CARE: This work addresses a shortage in the availability of the theranostic matched pair 203Pb/212Pb for clinical applications.

Footnotes

  • Published online Aug. 31, 2023.

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  • Received for publication May 4, 2023.
  • Revision received July 17, 2023.
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