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

• Main Authors: Santiago Andrés Brühlmann (Author), Martin Kreller (Author), Hans-Jürgen Pietzsch (Author), Klaus Kopka (Author), Constantin Mamat (Author), Martin Walther (Author), Falco Reissig (Author)
• Format: Book
• Published: MDPI AG, 2022-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 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 ¹³³La forms a perfectly matched theranostic pair of radionuclides with the therapeutic radionuclide ²²⁵Ac, 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 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 ¹³³La, formulated as [¹³³La]LaCl₃. After the 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 irradiation time to produce ¹³³La of high radionuclide purity (>99.5%) regarding labeling properties and side products.

Item Description

10.3390/ph15101167
1424-8247