Terbium-149 production: a focus on yield and quality improvement towards preclinical application

Abstract

Terbium-149 (T1/2 = 4.1 h, Eα = 3.98 MeV (16.7%), 28 µm range in tissue) is a radionuclide with potential for targeted alpha therapy. Due to the negligible emission of α-emitting daughter nuclides, toxicity to healthy tissue may be reduced in comparison with other α-particle emitters. In this study, terbium-149 was produced via 1.4 GeV proton irradiation of a tantalum target at the CERN-ISOLDE facility. The spallation products were mass separated and implanted on zinc-coated foils and, later, radiochemically processed. Terbium-149 was separated from the co-produced isobaric radioisotopes and the zinc coating from the implantation foil, using cation-exchange and extraction chromatographic techniques, respectively. At the end of separation, up to 260 MBq terbium-149 were obtained with > 99% radionuclidic purity. Radiolabeling experiments were performed with DOTATATE, achieving 50 MBq/nmol apparent molar activity with radiochemical purity > 99%. The chemical purity was determined by inductively coupled plasma–mass spectrometry measurements, which showed lead, copper, iron and zinc only at ppb level. The radiolabeling of the somatostatin analogue DOTATATE with [149Tb]TbCl3 and the subsequent in vivo PET/CT scans conducted in xenografted mice, showing good tumor uptake, further demonstrated product quality and its ability to be used in a preclinical setting.

Potential Biomedical Applications of Terbium-Based Nanoparticles (TbNPs): A Review on Recent Advancement

“…This creates better imaging and avoids the concerns of photobleaching by the traditional fluorophores. 11,12 Moreover, Terbium has higher penetrance, 13,14 facilitating deeper tissue visualization, 15−17 and tracking of disease progression 18,19 in a much more efficient manner. These special luminescence qualities can also be used as real-time medication release tracking techniques, providing accurate therapeutic management.…”

“…Terbium possesses a unique light emission mechanism, which is known as up conversion luminescence. , A process involves the absorption of low-energy photons and the emission of high-energy photons. This creates better imaging and avoids the concerns of photobleaching by the traditional fluorophores. , Moreover, Terbium has higher penetrance, , facilitating deeper tissue visualization, − and tracking of disease progression , in a much more efficient manner. These special luminescence qualities can also be used as real-time medication release tracking techniques, providing accurate therapeutic management. , Due to the magnetic properties of this metal, it can be utilized in magnetic resonance imaging (MRI) as a contrast agent for visualizing scan results with higher specificity at lower energy emissions owing to disease diagnosis and real-time monitoring.…”