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Description
Terbium is a unique element, as it provides a quadruplet of radionuclides suited for diagnostics and therapy in nuclear medicine [1]. Much success has been gained from the PSI-ISOLDE collaboration, with the collection and purification of 149Tb (α-emitter, T1/2 = 4.1 h – for potential therapy), used for preclinical therapy studies [2] and PET imaging [3], and 152Tb (β+-emitter, T1/2 = 17.5 h – for use in PET imaging), for preclinical [4] and clinical [5] PET imaging, respectively.
Following this success, further upgrades were required for the chemical separation system, as the ALARA (As Low As Reasonably Achievable) radiation safety principle should be adhered to – thereby, minimizing direct manipulation of the nuclides.
In 2017, mass-separated beams of 152Tb were implanted at ISOLDE-CERN into Zn-coated Au foils, using new shielded collection chamber. Collections of 152Tb lasted 4 to 6 hours and up to 600 MBq 152Tb could be shipped to PSI.
At PSI, the chemical separation system was performed using a new set up and manipulators in a hot cell. The foil containing the 152Tb was extracted from the Zn foils by dissolving them in HNO3/NH4NO3. The dissolved nuclides were loaded on to a macroporous strongly acidic cation exchange resin and 152Tb eluted using dilute α-hydroxyisobutyric acid (α-HIBA). As an addition, the product eluent was passed through a second resin, to ensure formulation of the product in chloride form.
152Tb was directly employed for radiolabeling of PSMA-617. PET/CT scans were performed with PC-3 PIP (PSMA-positive) tumor-bearing mice at different time points after injection of 152Tb-PSMA-617.
The successful experimental runs with the updated system has prepared the collaboration well for proposed extended preclinical imaging and therapy experiments in 2018, in the hope of finalizing the preclinical therapy study with 149Tb.
Support by ENSAR2 (EU H2020 project Nr. 654002) is gratefully acknowledged.
The authors thank the ISOLDE RILIS team for efficient Dy ionization and the ISOLTRAP-MR-TOF-MS team for beam characterisation.
[1] C. Müller et al., J. Nucl. Med. 53, 1951 (2012).
[2] C. Müller et al., Pharmaceuticals 7, 353 (2014).
[3] C. Müller et al., EJNMMI Radiopharmacy and Chemistry 1,5 (2016).
[4] C. Müller et al., EJNMMI Research 6, 35 (2016).
[5] R. Baum et al., Dalton Transactions, in press (2017).
