Efficient Production of the PET Radionuclide [sup.133]La for Theranostic Purposes in Targeted Alpha Therapy Using the [sup.134]Ba[sup.133]La Reaction

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 15; no. 10
• Main Authors: Brühlmann, Santiago Andrés, Kreller, Ma, Pietzsch, Hans-Jürgen, Kopka, Klaus, Mamat, Constantin, Walther, Ma, Reissig, Falco
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.09.2022
• Subjects: Chemical properties; Identification and classification; Methods; Radioisotopes; Radioisotopes in medical diagnosis; Radiotherapy; Germany
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph15101167

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, [sup.225] Ac provides all necessary physical and chemical properties for a successful clinical application, which has already been shown by [[sup.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 [sup.133] La forms a perfectly matched theranostic pair of radionuclides with the therapeutic radionuclide [sup.225] Ac, which itself can optimally be complexed by macropa as well. [sup.133] La was thus produced by cyclotron-based proton irradiation of an enriched [sup.134] Ba target. The target (30 mg of [[sup.134] Ba]BaCO[sub.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: [sup.135] La (0.4%), [sup.135m] Ba (0.03%), [sup.133m] Ba (0.01%), and [sup.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 [sup.133] La, formulated as [[sup.133] La]LaCl[sub.3] . After the complete decay of [sup.133] La, a remainder of ca. 4 kBq of long-lived [sup.133] Ba per 100 MBq of [sup.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 [sup.133] La of high radionuclide purity (>99.5%) regarding labeling properties and side products.