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Temperature-dependent cation-exchange separation of terbium tracer from gadolinium using α-hydroxyisobutyric acid: relevance to 161Tb production

This study demonstrates that increasing the column temperature to 70°C during cation-exchange chromatography with α-hydroxyisobutyric acid significantly improves the separation efficiency and recovery of terbium from bulk gadolinium, offering a promising method for purifying reactor-produced terbium-161, although the reported results are based on single-run nominal values pending further verification.

Original authors: Saadatu Bello, Ivan A. Ushakov, Lawal Zubairu, Kamal Babangida, Kabiru Hamzaa

Published 2026-09-08

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CC BY 4.0

Original authors: Saadatu Bello, Ivan A. Ushakov, Lawal Zubairu, Kamal Babangida, Kabiru Hamzaa

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

In the world of medicine, doctors are constantly searching for ways to treat cancer that are both powerful and precise. One promising approach involves using tiny amounts of radioactive material, known as radionuclides, which can be attached to molecules that seek out cancer cells. Once they arrive, these radioactive atoms release energy to destroy the tumor while sparing the healthy tissue around it. Among the many candidates for this job, an element called terbium-161 has generated significant excitement. It is special because it emits a mix of particles: some travel a short distance to kill cancer cells, while others produce signals that doctors can see on a camera, allowing them to track the treatment's progress. However, creating this useful isotope is a chemical puzzle. It is made inside a nuclear reactor by bombarding a different element, gadolinium, with neutrons. The problem is that the final product is mixed with a vast amount of the original gadolinium, and because these two elements are chemical cousins, they are incredibly difficult to pull apart. If the gadolinium is not removed, the final medicine becomes too weak to be effective.

Researchers at Tomsk Polytechnic University in Russia set out to solve this separation problem using a method that relies on heat. They wanted to see if changing the temperature of a chemical column could help separate the terbium from the gadolinium more cleanly. To do this, they did not use the actual medical isotope terbium-161, which is produced in a reactor, but instead used a safe, radioactive tracer of terbium to mimic its behavior. They mixed this tracer with a large amount of gadolinium and poured the solution into a column packed with a special resin, a material that acts like a sponge for ions. They then washed the column with a liquid called alpha-hydroxyisobutyric acid, which helps the elements move through the sponge at different speeds. The team tested this process at three different temperatures: 30, 50, and 70 degrees Celsius, carefully collecting the liquid that came out in small cups to see where each element ended up.

The results showed that heat played a crucial role in how well the two elements separated. At the lowest temperature of 30 degrees Celsius, the terbium and gadolinium came out of the column somewhat close together, with their paths overlapping. This meant that the final collection of terbium was still contaminated with about 2 percent of the unwanted gadolinium. As the researchers increased the temperature to 50 degrees, the separation improved significantly. The terbium moved through the column faster and stayed further away from the gadolinium, reducing the contamination to just 0.1 percent. The best performance was observed at 70 degrees Celsius. At this warmer temperature, the terbium emerged in a tight, concentrated group, while the gadolinium was held back much longer, staying in the column until a much later point. This resulted in a recovery of 99 percent of the terbium with the same minimal contamination of 0.1 percent.

The study confirms that heating the column makes the chemical separation process more efficient, allowing for a cleaner harvest of the desired element. The researchers found that at 70 degrees, the terbium could be collected in a volume of liquid between 40 and 65 milliliters, while the gadolinium did not start to appear until the liquid volume reached about 95 milliliters. This clear gap between the two elements is exactly what is needed to produce a high-quality medical isotope. However, the authors are careful to note that this was a laboratory experiment using natural gadolinium and a tracer, rather than the actual production of the medical isotope terbium-161. While the chemistry looks very promising, the team emphasizes that more work is needed to prove this method works on a larger scale with the specific enriched materials required for real-world medical use. For now, the study provides a clear, step-by-step demonstration that temperature is a powerful tool for untangling these difficult chemical mixtures.

Technical Summary: Temperature-Dependent Cation-Exchange Separation of Terbium from Gadolinium

Problem Statement
Terbium-161 ( $^{161}\text{Tb}$ ) is a promising radionuclide for targeted radionuclide therapy due to its emission of therapeutic beta particles, short-range conversion/Auger electrons, and gamma emissions suitable for imaging. The primary reactor-based production route involves the neutron capture reaction $^{160}\text{Gd}(n,\gamma)^{161}\text{Gd} \rightarrow ^{161}\text{Tb}$ . A significant challenge in this process is the efficient separation of trace amounts of the product ( $^{161}\text{Tb}$ ) from the bulk gadolinium target matrix. The chemical similarity of neighboring trivalent lanthanides complicates this separation, and inadequate removal of gadolinium can compromise the specific activity and chemical suitability of the final radiopharmaceutical. While cation-exchange chromatography using $\alpha$ -hydroxyisobutyric acid ( $\alpha$ -HIBA) is a known method, the specific influence of column temperature on the separation efficiency of terbium from gadolinium requires further characterization to optimize the process.

Methodology
This study investigated the effect of column temperature on the cation-exchange separation of a radioactive terbium tracer from gadolinium. The experimental setup utilized:

Resin: Dowex 50W-X8 strong-acid cation-exchange resin (ammonium form, 200–400 mesh).
Eluent: 0.3 M $\alpha$ -HIBA adjusted to pH 4.40 with $\text{NH}_4\text{OH}$ .
Targets: Natural gadolinium oxide ( $\text{Gd}_2\text{O}_3$ ) irradiated in the IRT-T research reactor (thermal neutron flux $\approx 1.7 \times 10^{14} \text{ n cm}^{-2} \text{ s}^{-1}$ ) served as the bulk matrix. A separately irradiated natural terbium oxide ( $\text{Tb}_4\text{O}_7$ ) tracer served as a surrogate for the $^{161}\text{Tb}$ fraction.
Procedure: Irradiated materials were dissolved in hydrochloric acid. Model solutions containing the gadolinium matrix and terbium tracer were loaded onto a 20 cm column. Elution was performed at three distinct temperatures: 30°C, 50°C, and 70°C.
Analysis: Fractions were collected at 5 mL intervals and analyzed using high-purity germanium (HPGe) gamma spectrometry. Terbium was quantified via the 298 keV peak ( $^{160}\text{Tb}$ ), and gadolinium via the 97 keV peak ( $^{153}\text{Gd}$ ).

Key Results
The study demonstrated that terbium consistently eluted before gadolinium across all tested temperatures. The separation profile and recovery metrics were temperature-dependent:

30°C: The terbium and gadolinium peaks showed partial overlap. The main terbium elution region was 30–35 mL, while gadolinium peaked at 45–50 mL. Nominal terbium recovery was 97%, with gadolinium contamination at 2.0%.
50°C: Separation improved, with the terbium peak shifting to 35–40 mL and gadolinium to 55–65 mL. Terbium recovery increased to 98%, and gadolinium contamination dropped to 0.1%.
70°C: This condition yielded the best separation. Terbium was distributed primarily between 40 and 65 mL, while gadolinium was retained significantly longer, extending to approximately 105 mL with the main activity region around 95 mL. Terbium recovery reached 99%, with gadolinium contamination remaining at 0.1%.

Significance and Claims
The paper positions this work as a laboratory-scale process-development experiment rather than a direct production validation. The authors explicitly state that the use of natural gadolinium and a terbium tracer means the study evaluates separation chemistry but does not provide direct measurements of $^{161}\text{Tb}$ production yield, specific activity, or radionuclide purity.

The primary significance of the study is the identification of 70°C as a promising operating temperature for the Dowex 50W-X8/ $\alpha$ -HIBA system, offering the highest nominal recovery (99%) and lowest contamination (0.1%). The authors conclude that while the results are encouraging for future process development, the method requires further validation before clinical application. This includes testing with enriched $^{160}\text{Gd}$ , performing replicate experiments to establish statistical significance, conducting complete detector calibration, quantifying elemental impurities (e.g., via ICP-MS), and verifying radiolabeling performance with chelators like DOTA. The study serves as a descriptive basis for optimizing parameters in future automated hot-cell processing for $^{161}\text{Tb}$ production.

Technical Summary: Temperature-Dependent Cation-Exchange Separation of Terbium from Gadolinium

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