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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.

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