Efficient Production of the PET radionuclide ¹³³La for Theranostic Purposes in Targeted Alpha Therapy using the ¹³⁴Ba(p,2n)¹³³La Reaction

Targeted Alpha Therapy is a research field of highest interest in specialized radionuclide therapy. Over the last decades, several alpha-emitting radionuclides have entered and left research topics towards their clinical translation. Especially, 225Ac provides all necessary physical and chemical properties for a successful clinical application, which has already been shown by [225Ac]Ac PSMA 617. While PSMA 617 carries the DOTA as the complexing agent, the chelator macropa as macrocyclic alternative provides even more beneficial properties regarding labeling and complex stability in vivo. Lanthanum-133 is an excellent positron-emitting diagnostic lanthanide to radiolabel macropa-functionalized therapeutics, since 133La forms a perfect matched theranostic pair of radionuclides with the therapeutic radionuclide actinium-225 which itself can optimally be complexed by macropa as well. 133La was thus produced by cyclotron-based proton irradiation of an enriched 134Ba target. The target (30 mg of [134Ba]BaCO3) was irradiated for 60 min at 22 MeV and 10-15 µA beam current. Irradiation side products in the raw target solution were identified and quantified: 135La (0.4%), 135mBa (0.03%), 133mBa (0.01%) and 133Ba (0.0004%). The subsequent work-up and anion-exchange-based product purification process took approx. 30 min and led to a total amount of (1.2 – 1.8) GBq (decay-corrected to EOB) of 133La, formulated as [133La]LaCl3. After complete decay of 133La, a remainder of ca. 4 kBq of long-lived 133Ba per 100 MBq of 133La was detected and rated as uncritical regarding personal dose and waste management. Subsequent radiolabeling was successfully performed with previously published macropa-derived PSMA inhibitors at a micromolar range (quantitative labeling at 1 µM) and evaluated by radio-TLC and radio-HPLC analyses. The scale up to radioactivity amounts that are needed for clinical application purposes would be easy to achieve by increasing target mass, beam current and/or irradiation time to produce 133La of high radionuclide purity (>99.5%) regarding labeling properties and side products.