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

Abstract

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 hig...

A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68Ga, 44Sc, 177Lu and 161Tb

“…The radiochemical separation method for the routine production of n.c.a. 177 Lu on an industrial scale for medical applications is described in [162]. The reported separation method is capable of the separation of 177 Lu and 176 Yb in a mass ratio of 1:10 2 to 1:10 10 .…”

“…A two-column separation system has been applied for the separation of terbium from enriched gadolinium target material [162]. After dissolution of target and the loading of the radionuclides onto a Sykam cation exchange resin column, α-HIBA separation system is used to separate terbium from macro amounts of gadolinium target material.…”

“…LN3 resin is an extraction resin containing acidic organophosphorus extractants [163], which can be used for the separation of complexing agent (α-HIBA) from Tb and, furthermore, ensures elution of 161 Tb in a small volume of dilute HCl. The use of LN3 resin, as suggested by Gracheva et al, is used as the last step of 161 Tb production to avoid the lengthy evaporation step [162], previously needed to obtain the final solution in dilute acid. This procedure cannot replace the evaporation step in the 177 Lu separation process, however, due to the high distribution coefficient of Lu in dilute acids on LN3 resin [164].…”

“…On the other hand, the decay product of 161 Tb is Dy, which could well interfere with Tb labeling. The radiolabeling yield of 161 Tb-DOTA has been investigated and it was shown that even after two weeks, the molar activity of the product was sufficient for potential clinical application [162]. Comparison studies have shown that 161 Tb-and 177 Lu-DOTATOC (solutions in saline at room temperature) are stable over 24 h in the presence of a stabilizer (L-ascorbic acid).…”

“…Tb 161 Tb is not yet commercially available and is not produced based on pharmaceutical legislation in EU-GMP regulations. It was demonstrated that the 161 TbCl 3 final product is suitable for pharmaceutical use without requiring further purification and sterilization [162]. Due to the similar chemical characteristics of 161 Tb and 177 Lu, the synthesis module protocols commonly used for 177 Lu synthesis can be directly adapted for the production of 161 Tb radiopharmaceuticals.…”