The chemical separation of terbium for applications in nuclear medicine
Creators: name: WEBSTER, BENJAMIN LUKE
Publisher: name: University of Surrey
Year: 2022

description: "This research aimed to develop robust and thorough chemical separation procedures to support the development of novel diagnostic, therapeutic and/or theranostic nuclear medicine using several terbium isotopes, 149Tb, 152Tb, 155Tb and 161Tb. Little explored extraction chromatography resins were investigated for the separation of these terbium isotopes from other lanthanide impurities which are present after their production via various routes. Stable element standards and ICP-QQQ-MS analysis were used throughout method development experiments and, when possible, the developed methods were validated using radioactive terbium samples produced via the associated production route.
description: In a mass-separated, proton-induced spallation source of 155Tb (t½ = 5.32 d), a significant polyatomic 139Ce16O impurity (t½ = 136.7 d) remained. Selective oxidation of cerium using NaBrO3 was investigated and was shown to markedly change the chromatographic behaviour of cerium whilst leaving terbium unaffected. Separation of Tb(III) from Ce(IV) was studied separately on three extraction chromatography resins and an anion exchange resin. Through a series of batch separation and column separation experiments, UTEVA extraction chromatography resin (Triskem International) was shown to provide the best separation out of the four studied resins. A column-based UTEVA method was developed and formed an essential part of a larger processing procedure that was used to purify 155Tb sources that are produced by proton-induced spallation. This procedure was shown to be capable of isolating high purity 155Tb (&gt;99% radiological purity) and subsequently facilitated SPECT imaging studies, nuclear data measurements and a world-first primary standardisation of 155Tb.
description: Further study identified that this UTEVA method was not capable of isolating terbium from other lanthanide impurities present in mass-separated, proton induced spallation sources of 149Tb, 152Tb and 155Tb. The presence of these other long-lived or stable impurities would reduce the specific activity of a radiopharmaceutical. This necessitated investigation into an alternative method which was capable of isolating terbium from all other lanthanide elements.
description: A series of batch and column separation experiments led to the development of a semiautomated, three-step column separation method which utilised the LN extraction chromatography resin (Triskem International). The method was capable of isolating terbium from trace quantities of all other lanthanide impurities. An ICP-QQQ-MS method, which utilised two quadrupole mass filters and an O2 reaction cell, was used throughout the method development process to ensure accurate percentage recovery and purity information could be derived by removing tailing and polyatomic measurement interferences. Using the developed LN resin method, high purity terbium fractions (&gt;90% terbium recovery, &gt;99% terbium purity) could be isolated in &lt;120 minutes using a 200×7 mm LN resin column and a 0.5 mL/min mobile phase flowrate. This method results in a separation of comparable quality to the commonly used α-HIBA, cation exchange methods. Initial studies using a smaller LN resin column (50×5 mm) reduced the separation time significantly with minimal impact on the terbium recovery and purity (&lt;15 mins). Use of these smaller columns should be considered for the shorter-lived terbium isotopes, 149Tb (t½ = 4.12 h) and 152Tb (t½ = 17.5 h) to reduce losses of the isotope due to radioactive decay.
description: The separation of trace quantities of terbium (µg) from bulk quantities of gadolinium and europium (≤100 mg) was then studied separately using the same stepwise LN resin method (200×7 mm column) to assess whether the method was also suitable for processing terbium produced in cyclotron or nuclear reactor facilities. The capacity of the resin was derived using a novel batch separation method (6.89 mg – 12.48mg Gd/mL of LN resin) and was shown to be a limiting factor for bulk-trace lanthanide..."