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

摘要

Abstract BackgroundIn 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.MethodsThe 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.ResultsA 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.ConclusionThe 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.