Radionuclide generator-based production of therapeutic 177Lu from its long-lived isomer 177mLu

Rupali Bhardwaj; Hubert Th Wolterbeek; Antonia G Denkova; Pablo Serra-Crespo

doi:10.1186/s41181-019-0064-5

Radionuclide generator-based production of therapeutic ¹⁷⁷Lu from its long-lived isomer ^177mLu

EJNMMI Radiopharm Chem. 2019 Jul 15;4(1):13. doi: 10.1186/s41181-019-0064-5.

Authors

Rupali Bhardwaj^{1

2}, Hubert Th Wolterbeek¹, Antonia G Denkova¹, Pablo Serra-Crespo³

Affiliations

¹ Applied Radiation and Isotopes, Department of Radiation Science and Technology, Faculty of Applied Sciences, Technical University Delft, Mekelweg 15, 2629 JB, Delft, The Netherlands.
² Catalysis Engineering, Department of Chemical Engineering, Faculty of Applied Sciences, Delft University of Technology, Van der Maasweg 9, 2629, HZ, Delft, The Netherlands.
³ Applied Radiation and Isotopes, Department of Radiation Science and Technology, Faculty of Applied Sciences, Technical University Delft, Mekelweg 15, 2629 JB, Delft, The Netherlands. P.SerraCrespo@tudelft.nl.

Abstract

Background: In this work, a lutetium-177 (¹⁷⁷Lu) production method based on the separation of nuclear isomers, ^177mLu & ¹⁷⁷Lu, is reported. The ^177mLu-¹⁷⁷Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction.

Methods: The ^177mLu cations were complexed with DOTA & DOTATATE and kept at 77 K for periods of time to allow ¹⁷⁷Lu production. The freed ¹⁷⁷Lu ions produced via internal conversion of ^177mLu were then extracted in dihexyl ether using 0.01 M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35 days.

Results: A maximum ¹⁷⁷Lu/^177mLu activity ratio of 3500 ± 500 was achieved with [^177mLu]Lu-DOTA complex, in comparison to ¹⁷⁷Lu/^177mLu activity ratios of 1086 ± 40 realized using [^177mLu]Lu-DOTATATE complex. The ¹⁷⁷Lu-^177mLu separation was found to be affected by the molar ratio of lutetium and DOTA. A ¹⁷⁷Lu/^177mLu activity ratio up to 3500 ± 500 was achieved with excess DOTA in comparison to ¹⁷⁷Lu/^177mLu activity ratio 1500 ± 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the ¹⁷⁷Lu ion extraction efficiency, decreases from 95 ± 4% to 58 ± 2% in the presence of excess DOTA.

Conclusion: The reported method resulted in a ¹⁷⁷Lu/ ^177mLu activity ratio up to 3500 after the separation. This ratio is close to the lower end of ¹⁷⁷Lu/^177mLu activity ratios, attained currently during the direct route ¹⁷⁷Lu production for clinical applications (i.e. 4000-10,000). This study forms the basis for further extending the liquid-liquid extraction based ^177mLu-¹⁷⁷Lu separation in order to lead to a commercial ^177mLu/¹⁷⁷Lu radionuclide generator.

Keywords: 177Lu production; 177mLu/177Lu radionuclide generator; Lutetium-177; Nuclear isomer separation.

Grants and funding

HTSM 13306/Stichting voor de Technische Wetenschappen