Abstract
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.