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.