177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β− emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals.

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Background In this work, a lutetium-177 ( 177 Lu) production method based on the separation of nuclear isomers, 177m Lu & 177 Lu, is reported. The 177m Lu- 177 Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction. Methods The 177m Lu cations were complexed with DOTA & DOTATATE and kept at 77 K for periods of time to allow 177 Lu production. The freed 177 Lu ions produced via internal conversion of 177m Lu 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 177 Lu/ 177m Lu activity ratio of 3500 ± 500 was achieved with [ 177m Lu]Lu-DOTA complex, in comparison to 177 Lu/ 177m Lu activity ratios of 1086 ± 40 realized using [ 177m Lu]Lu-DOTATATE complex. The 177 Lu- 177m Lu separation was found to be affected by the molar ratio of lutetium and DOTA. A 177 Lu/ 177m Lu activity ratio up to 3500 ± 500 was achieved with excess DOTA in comparison to 177 Lu/ 177m Lu activity ratio 1500 ± 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the 177 Lu ion extraction efficiency, decreases from 95 ± 4% to 58 ± 2% in the presence of excess DOTA. Conclusion The reported method resulted in a 177 Lu/ 177m Lu activity ratio up to 3500 after the separation. This ratio is close to the lower end of 177 Lu/ 177m Lu activity ratios, attained currently during the direct route 177 Lu production for clinical applications (i.e. 4000–10,000). This study forms the basis for further extending the liquid-liquid extraction based 177m Lu- 177 Lu separation in order to lead to a commercial 177m Lu/ 177 Lu radionuclide generator. Electronic supplementary material The online version of this article (10.1186/s41181-019-0064-5) contains supplementary material, which is available to authorized users.

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