P-260 - Validating the impact of metal contaminants on the radiolabeling of DOTATATE with 161Tb

Research outputpeer-review


Objectives: The radiolanthanide 161Tb is a promising β–-emitter for targeted radionuclide therapy due to its favorable decay properties (T1/2= 6.89 d, E_(β_av^- ) = 154 keV). Compared to 177Lu (T1/2= 6.65 d, E_(β_av^- ) = 134 keV), an increased therapeutic effect can be expected due a significant amount of co-emitted short-ranged Auger/conversion electrons [1]. Production and quality assessment of 161Tb are currently being carried out at the Belgian Nuclear Research Centre. As previous studies have already demonstrated the detrimental effect of metal contaminants on the radiolabeling of DOTA chelators with 177Lu [2], it is important to closely monitor the chemical purity of 161Tb. To further corroborate this, we aim to demonstrate the influence of metal impurities on the radiolabeling of DOTATATE with 161Tb under typical labeling conditions.
Methods: Radiolabelings were performed with 20 MBq of 161Tb or 177Lu at a molar activity of 100 MBq/nmol DOTATATE, in 150 µL of 0.15 M sodium acetate buffer (pH 4.7) and at 95 °C for 15 min. For both 161Tb and 177Lu, the impact of Cu2+, Zn2+, Pb2+, Fe3+, the target material and the daughter isotope was evaluated. For each metal, metal/radionuclide molar ratios ranging from 0.5 to 5 were tested. All reactions were performed in quadruplicate and radiochemical yields (RCYs) were assessed by radio-TLC analysis using a 0.2 M citrate buffer (pH 5) as the mobile phase.
Results: The quality of the produced 161Tb is routinely assessed by the radiolabeling of DOTATATE at a molar activity of 180 MBq/nmol, leading to radiochemical yields (RCYs) of ≥98% as determined by radio-TLC. At 100 MBq/nmol, the presence of transition metals (except for Hf4+) or lanthanides showed a notable impact on the RCY for metal/161Tb molar ratios ≤2.5. Similar results were obtained with 177Lu at this molar activity. In case of 5 molar equivalents of the metal contaminants, the RCYs dropped below 20%.
Conclusions: The results clearly demonstrated the impact of metal contaminants on the radiolabeling of DOTA with 161Tb or 177Lu. This illustrates the importance of the chemical purity of the radiolanthanides, especially for the radiolabeling of DOTA at high molar activities. Furthermore, 161Tb has a competing daughter (161Dy), which is an important consideration in view of determining its shelf-life.
[1] (a) Müller, C., Umbricht, C. A., Gracheva, N. et al. Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 2019, 46, 1919–1930. (b) Borgna, F., Haller, S., Rodriguez J. M. M. et al. Combination of terbium-161 with somatostatin receptor antagonists-a potential paradigm shift for the treatment of neuroendocrine neoplasms. Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 1113-1126.
[2] Asti, M., Tegoni, M., Farioli, D. et al. Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions. Nuc. Med. Biol. 2012, 39, 509–517.
Original languageEnglish
Title of host publicationNuclear Medicine and Biology
Subtitle of host publicationAbstracts of the International Symposium on Radiopharmaceutical Sciences iSRS 2023
Number of pages2
StatePublished - 1 Dec 2023
Event2023 - iSRS: 25th International Symposium of Radiopharmaceutical Sciences - Hawai'i Convention Center, Honolulu
Duration: 22 May 202326 May 2023

Publication series

NameNuclear Medicine and Biology
ISSN (Print)0969-8051


Conference2023 - iSRS
Country/TerritoryUnited States
Internet address

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