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.
Highlights
In this work, a lutetium-177 (177Lu) production method based on the separation of nuclear isomers, 177mLu & 177Lu, is reported
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
Summary
A lutetium-177 (177Lu) production method based on the separation of nuclear isomers, 177mLu & 177Lu, is reported. The current state of the art of 99mTc, 188Re, 68Ga pharmaceuticals owes their existence largely to the availability of their corresponding radionuclide generators (Roesch & Riss, 2010; Pillai et al, 2012). They offer continuous, on-site and on-demand isolation of a short-lived daughter radionuclide. The long half-life of 177mLu (160.44 days) can potentially lead to on-site and on-demand 177Lu supply for a long period of time without the need of weekly irradiations in nuclear reactor (De Vries & Wolterbeek, 2012; Bhardwaj et al, 2017). The development of 177mLu/177Lu radionuclide generator needs to tackle the great challenge of separating the physically and chemically alike nuclear isomers 177Lu and 177mLu
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