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

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. Electronic supplementary material The online version of this article (10.1186/s41181-019-0064-5) contains supplementary material, which is available to authorized users.

Separation of 44mSc/44gSc Nuclear Isomers Based on After-Effects

“…The trend of the percent of the daughter release (*per the portion of conversion, in the cases of IT and β decay, or per the portion of EC) depending on the Z -number of the daughter for 212 Bi, 177g Lu, 152 Sm, 166 Ho, 140 Pr, 111 Cd, − and 44g Sc. The black curve includes the data on 44g Sc-DOTATOC shown in this work, and the red curve includes the data on 44g Sc-DOTATATE reported by Huclier-Markai et al, which are in agreement with our data.…”

“…The same case was recorded for [ 152 Eu]Eu-DTPA investigated by PAC; its daughter 152 Sm was fully released from the initial complex. 15 Bhardwaj et al reported the design of a 177m Lu/ 177g Lu radionuclide generator based on after-effects, 10,24 with a yield of 95 ± 4%. 10 A similar case was noted with the 140 Nd/ 140 Pr pair, whereby the daughter 140 Pr was released from the initial complex with DOTATOC with a 93 ± 5% release.…”

“…15 Bhardwaj et al reported the design of a 177m Lu/ 177g Lu radionuclide generator based on after-effects, 10,24 with a yield of 95 ± 4%. 10 A similar case was noted with the 140 Nd/ 140 Pr pair, whereby the daughter 140 Pr was released from the initial complex with DOTATOC with a 93 ± 5% release. 12 By contrast, a study on 111 In (EC, 100%) complexes with DTPA by PAC showed that only a partial release of its daughter 111 Cd is observed, and ≈50% of the complexes remained stable.…”

“…The aforementioned design of the generators describes the distribution of the daughter radionuclide forms over different phases, which allows for the determination of only the macro parameters. However, by choosing the specific chemical form of the parent radionuclide and setting appropriate conditions according to the macro parameters, such processes can be investigated at the micro level (such as in refs − ).…”

Patient-specific dosimetry adapted to variable number of SPECT/CT time-points per cycle for $$^{177}$$Lu-DOTATATE therapy

“…The treatment consists to intravenously inject somatostatin analogue radiolabelled with Lu ( Lu-DOTATATE). The treatment efficacy was demonstrated in the NETTER study [ 1 ], and its use was approved by the FDA in 2018 [ 3 ]. The standardized treatment is composed of four cycles of 7.4 GBq injections, about 8 weeks apart.…”