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

BackgroundIn this work, a lutetium-177 (Lu-177) production method based on the separation of nuclear isomers, Lu-177m & Lu-177, is reported. The Lu-177m-Lu-177 separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction.MethodsThe Lu-177m cations were complexed with DOTA & DOTATATE and kept at 77K for periods of time to allow Lu-177 production. The freed Lu-177 ions produced via internal conversion of Lu-177m were then extracted in dihexyl ether using 0.01M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35days.ResultsA maximum Lu-177/Lu-177m activity ratio of 3500500 was achieved with [Lu-177m]Lu-DOTA complex, in comparison to Lu-177/Lu-177m activity ratios of 1086 +/- 40 realized using [Lu-177m]Lu-DOTATATE complex. The Lu-177-Lu-177m separation was found to be affected by the molar ratio of lutetium and DOTA. A Lu-177/Lu-177m activity ratio up to 3500 +/- 500 was achieved with excess DOTA in comparison to Lu-177/Lu-177m activity ratio 1500 +/- 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the Lu-177 ion extraction efficiency, decreases from 95 +/- 4% to 58 +/- 2% in the presence of excess DOTA.Conclusion The reported method resulted in a Lu-177/ Lu-177m activity ratio up to 3500 after the separation. This ratio is close to the lower end of Lu-177/Lu-177m activity ratios, attained currently during the direct route Lu-177 production for clinical applications (i.e. 4000-10,000). This study forms the basis for further extending the liquid-liquid extraction based Lu-177m-Lu-177 separation in order to lead to a commercial Lu-177m/Lu-177 radionuclide generator.