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Description
Terbium is a unique element in that it includes a quadruplet of radioisotopes suitable for diagnostics and therapy in nuclear medicine [1]. With their characteristics, it can contribute to the theragnostics concept, where one can treat what one images. 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, 3] and PET imaging [4], and 152Tb (β+-emitter, T1/2 = 17.5 h – for use in PET imaging), for preclinical [5] and clinical [6] PET imaging, respectively.
Two one-week campaigns to produce 149Tb took place in November 2021 and March 2022, respectively. Collections were performed overnight using Zn-coated gold foils. The foils, containing the desired product and its 149 isobars were transported to Paul Scherrer Institute for processing. The chemical separations were performed using an updated method. Usable product (yields around 100 MBq) were produced using a two-column separation system in a hot cell, allowing the labelling of 149Tb to somatostatin analogues and its use for preclinical studies.
149Tb-somatostatin analogues were labelled at >98% radiochemical purity at up to 20 MBq/nmol apparent molar activity. Mice, bearing AR42J tumours that express the somatostatin receptor, were injected twice (two consecutive days with 5 MBq each) for larger tumours, while mice with small tumours were injected once only. The mice were monitored over several weeks with regard to the tumour growth and body weight. The tumour growth was significantly delayed in all cases, while the treatment was well tolerated with no signs of obvious side effects. In addition, in vitro studies were performed to ascertain dose-dependent and receptor-specific cell killing upon exposure of the cells to 149Tb-labelled somatostatin analogues. More detailed results will be presented.
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 characterization.
[1] Müller et al., J. Nucl. Med. 53, 1951 (2012).
[2] Müller et al., Pharmaceuticals 7, 353 (2014).
[3] Umbricht et al., Scientific Reports 9, 17800 (2019).
[4] Müller et al., EJNMMI Radiopharmacy and Chemistry 1,5 (2016).
[5] Müller et al., EJNMMI Research 6, 35 (2016).
[6] Baum et al., Dalton Transactions 46, 14638 (2017).