Scalability study on [¹³³La]LaCl₃ production with a focus on potential clinical applications

In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter ²²⁵Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide to form a matched pair with ²²⁵Ac is still open, and ¹³³La features attractive radiation properties to claim this place. However, in order to enable its translation into clinical use, upscaling of the production of this PET radionuclide is needed.

A study on optimal irradiation parameters, separation conditions and an exhaustive product characterization was carried out. In this framework, a proton irradiation of 2 h, 60 µA and 18.7 MeV produced ¹³³La activities of up to 10.7 GBq at end of bombardment. In addition, the performance of four different chromatographic resins were tested and two optimized purification methods presented, taking approximately 20 min with a ¹³³La recovery efficiencies of over 98%, decay corrected. High radionuclide purity and apparent molar activity was proved, of over 99.5% and 120 GBq/µmol, respectively, at end of purification. Furthermore, quantitative complexation of PSMA-617 and mcp-M-PSMA were obtained with molar activities up to 80 GBq/µmol. In addition, both ¹³³La-radioconjugates offered high stability in serum, of over (98.5 ± 0.3)% and (99.20 ± 0.08)%, respectively, for up to 24 h. A first dosimetry estimation was also performed and it was calculated that an ¹³³La application for imaging with between 350 and 750 MBq would only have an effective dose of 2.1-4.4 mSv, which is comparable to that of ¹⁸F and ⁶⁸Ga based radiopharmaceuticals.

In this article we present an overarching study on ¹³³La production, from the radiation parameters optimization to a clinical dose estimation. Lanthanum-133 activities in the GBq range could be produced, formulated as [¹³³La]LaCl₃ with high quality regarding radiolabeling and radionuclide purity. We believe that increasing the ¹³³La availability will further promote the development of radiopharmaceuticals based on macropa or other chelators suitable for ²²⁵Ac.