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Terbium-149 was proposed as an attractive candidate for Targeted Alpha Therapy (TAT) in the late 1990’s [1], due to its favourable physical decay properties (T1/2 = 4.1 h, Eα = 3.97 MeV, 17%; Eβ+ mean = 720 keV, 7%) [2]. Preclinical studies have demonstrated its therapeutic potential [3-5], however, it was also demonstrated that it can be used for positron emission tomography (PET) [4]. The absence of daughter nuclides emitting relevant quantities of α-particles make it particularly promising, despite its current limited development.
Terbium-149 was produced at ISOLDE/CERN via spallation induced in a tantalum target using high-energy (1.4 GeV) protons, followed by effusion, release and ionization of the spallation products, which were mass-separated online. The mass 149 isobars were collected in zinc-coated gold/platinum/tantalum foils and shipped to PSI for processing. Terbium-149 was chemically separated from its isobaric impurities, as well as the collection material, using cation exchange and extraction chromatography, employing an optimized process as compared to the procedure previously reported [5]. The quality of the radionuclide produced was assessed analytically and by means of radiolabelling experiments.
Up to 1.9 GBq terbium-149 were collected and transported in an experimental campaign in 2024, with ~850 MBq activity received upon arrival at PSI. The four-hour radiochemical separation process yielded up to 400 MBq final product. The product radiochemical purity was measured by γ-spectrometry and found to be 99.8%. Quality control was performed using DOTATATE, which was successfully labeled at molar activities up to 50 MBq/nmol with >99% radiochemical purity [5]. The chemical purity was further proven by ICP-MS measurements, which showed lead, copper, iron and zinc contaminants at ppb levels.
The collection of mass separated-terbium-149 and radiochemical separation process has steadily improved over the years, such that higher activities can be collected and isolated, while the quality of product can ensure more efficient labelling of tumour-targeting small molecules towards preclinical therapy studies.
The authors thank CERN and PSI radiation safety and logistics teams, as well as Nicole Pereira da Lima (USP - IPEN/CNEN, Brazil) and Wiktoria Wojtaczka (KU Leuven, Belgium) for assistance in collections.
[1] Allen. Australasian Radiology 1999, 43:480.
[2] Singh & Chen. Nuclear Data Sheets 2022, 185:2
[3] Beyer et al. Radiochim Acta 2002, 90:247.
[4] Müller et al. EJNMMI Radiopharm Chem 2016, 1:5.
[5] Umbricht et al. Sci Rep 2019, 9:17800.
[6] Favaretto et al. Sci Rep 2024,14:3284
