Efficient Production of the PET Radionuclide (133)La for Theranostic Purposes in Targeted Alpha Therapy Using the (134)Ba(p,2n)(133)La 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, (225)Ac provides all necessary physical and chemical properties for a successful clinical application, which has already been shown by [(225)Ac]Ac-PSMA-617. While PSMA-617 carries the DOTA moiety as the complexing agent, the chelator macropa as a 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 (133)La forms a perfectly matched theranostic pair of radionuclides with the therapeutic radionuclide (225)Ac, which itself can optimally be complexed by macropa as well. (133)La was thus produced by cyclotron-based proton irradiation of an enriched (134)Ba target. The target (30 mg of [(134)Ba]BaCO(3)) 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: (135)La (0.4%), (135m)Ba (0.03%), (133m)Ba (0.01%), and (133)Ba (0.0004%). The subsequent workup 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 end of bombardment) of (133)La, formulated as [(133)La]LaCl(3). After the complete decay of (133)La, a remainder of ca. 4 kBq of long-lived (133)Ba per 100 MBq of (133)La 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 irradiation time to produce (133)La of high radionuclide purity (>99.5%) regarding labeling properties and side products.