Production and characterization of no-carrier-added 161Tb as an alternative to the clinically-applied 177Lu for radionuclide therapy

• Published in: EJNMMI radiopharmacy and chemistry 2019-07, Vol.4 (1), p.12-12, Article 12
• Main Authors: Gracheva, Nadezda, Müller, Cristina, Talip, Zeynep, Heinitz, Stephan, Köster, Ulli, Zeevaart, Jan Rijn, Vögele, Alexander, Schibli, Roger, van der Meulen, Nicholas P.
• Format: Article
• Language: English
• Subjects: 161Tb; Acids; Auger/conversion electrons; Cancer; Cancer therapies; Chemical behavior; Chemistry; Dosimetry; DOTA; Drug dosages; Imaging; Medicine; Medicine & Public Health; Molecular Medicine; Neuroendocrine tumors; Neutron radiation; Nitrates; Nuclear Chemistry; Nuclear Medicine; Peptides; Pharmacotherapy; Purification method; Radiation therapy; Radiology; Research Article; Resins; Somatostatin; Somatostatin analogues; Studies; Therapeutic applications; Vitamin B
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-019-0063-6

Background 161 Tb is an interesting radionuclide for cancer treatment, showing similar decay characteristics and chemical behavior to clinically-employed 177 Lu. The therapeutic effect of 161 Tb, however, may be enhanced due to the co-emission of a larger number of conversion and Auger electrons as compared to 177 Lu. The aim of this study was to produce 161 Tb from enriched 160 Gd targets in quantity and quality sufficient for first application in patients. Methods No-carrier-added 161 Tb was produced by neutron irradiation of enriched 160 Gd targets at nuclear research reactors. The 161 Tb purification method was developed with the use of cation exchange (Sykam resin) and extraction chromatography (LN3 resin), respectively. The resultant product ( 161 TbCl 3 ) was characterized and the 161 Tb purity compared with commercial 177 LuCl 3 . The purity of the final product ( 161 TbCl 3 ) was analyzed by means of γ-ray spectrometry (radionuclidic purity) and radio TLC (radiochemical purity). The radiolabeling yield of 161 Tb-DOTA was assessed over a two-week period post processing in order to observe the quality change of the obtained 161 Tb towards future clinical application. To understand how the possible drug products (peptides radiolabeled with 161 Tb) vary with time, stability of the clinically-applied somatostatin analogue DOTATOC, radiolabeled with 161 Tb, was investigated over a 24-h period. The radiolytic stability experiments were compared to those performed with 177 Lu-DOTATOC in order to investigate the possible influence of conversion and Auger electrons of 161 Tb on peptide disintegration. Results Irradiations of enriched 160 Gd targets yielded 6–20 GBq 161 Tb. The final product was obtained at an activity concentration of 11–21 MBq/μL with ≥99% radionuclidic and radiochemical purity. The DOTA chelator was radiolabeled with 161 Tb or 177 Lu at the molar activity deemed useful for clinical application, even at the two-week time point after end of chemical separation. DOTATOC, radiolabeled with either 161 Tb or 177 Lu, was stable over 24 h in the presence of a stabilizer. Conclusions In this study, it was shown that 161 Tb can be produced in high activities using different irradiation facilities. The developed method for 161 Tb separation from the target material yielded 161 TbCl 3 in quality suitable for high-specific radiolabeling, relevant for future clinical application.