Production of (177)Lu for Targeted Radionuclide Therapy: Available Options

Abstract

Background: This review provides a comprehensive summary of the production of (177)Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of (177)Lu having the required quality for preparation of a variety of (177)Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of (177)Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success.

Methods: While both "direct" and "indirect" reactor production routes offer the possibility for sustainable (177)Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies.

Results: This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future.

Conclusion: A broad understanding and discussion of the issues associated with (177)Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of (177)Lu-labeled radiopharmaceuticals, but also help future developments.

Keywords: Carrier-added (CA) 177Lu; Extraction chromatography (EXC); Neutron irradiation; No carrier-added (NCA) 177Lu; Radiochemical separation; Targeted radionuclide therapy (TRT).

Fig. 1

Simplified decay scheme of ¹⁷⁷Lu

Fig. 2

Two different routes for reactor production of ¹⁷⁷Lu

Fig. 3

Variation of the specific activity of ¹⁷⁷Lu, theoretically calculated using k = 1.5, 2.0 and 2.5, with the duration of irradiation when the enriched (82 % in ¹⁷⁶Lu) target is irradiated at a thermal neutron flux of 1.2 × 10¹⁴ n.cm^-2.s^-1r

Fig. 4

Comparison of variation of calculated ¹⁷⁷Lu specific activity taking into account the burn-up correction with that calculated without burn-up correction (both considering k =2)

Fig. 5

Calculated yields of ¹⁷⁷Lu activity produced via the indirect route at different neutron fluxes and different irradiation times

Fig. 6

Front-end enriched ¹⁷⁶Yb target removal step [68]. The first step involves the separation of the enriched Yb target from ¹⁷⁷Lu using LN2 resin, and the second step constitutes the concentration and acid adjustment of the Lu-rich eluate using a chromatography column containing DGA resin

Fig. 7

Primary NCA ¹⁷⁷Lu separation step [68]. The first step involves the purification of ¹⁷⁷Lu from micro amounts of Yb using LN2 resin, and the second step using DGA resin is for the concentration and acid adjustment of the ¹⁷⁷Lu eluate

Fig. 8

Secondary NCA ¹⁷⁷Lu separation step [68]. This process is essential for removing adventitious impurities from the ¹⁷⁷Lu

Fig. 9

Schematic diagram of the electrochemical setup used for the production of ¹⁷⁷Lu [82]

Fig. 10

Production flow chart used for the isolation of NCA ¹⁷⁷Lu following electrochemical separation technique [82]

Fig. 11

A typical gamma spectrum of a ¹⁷⁷Lu sample aliquot obtained from the (n,γ) ¹⁷⁷Lu production route recorded immediately (a) after radiochemical processing and (b) after 70-day decay

Fig. 12

Paper chromatography pattern of ¹⁷⁷Lu³⁺

Fig. 13

HPLC pattern of ¹⁷⁷Lu³⁺