Efficient Production of the PET Radionuclide Lanthanum-133

Ziel/Aim:

Targeted Alpha Therapy is a research field of highest interest in specialized radionuclide therapy. In particular the radionuclide actinium-225 provides all necessary physical and chemical properties for a successful clinical application. Although the macropa chelator has shown beneficial properties regarding labeling and stability in vivo as compared with DOTA, the former lacks an imaging counterpart to actinium-225. On the other hand, lanthanum is a perfect surrogate for actinium. The imaging properties of the β+-emitter lanthanum-133 makes it an attractive candidate as a theranostic matched pair to actinium-225. This project aims at the cyclotron-based production of lanthanum-133 with high radionuclidic purity for theranostic purposes.
Methodik/Methods:
Silver discs were filled with [Ba-134]BaCO3 and capped with a platinum foil. One-hour proton irradiations (18.6 MeV, 15 µA) were performed with the HZDR TR-FLEX (ACSI) cyclotron. The powder target was then opened and the dry solid dissolved in HNO3. Separation was carried out with branched DGA cartridge, although other anion-exchange resins are also under investigation. The fractions containing Ba were collected for recovery. Test radiolabeling of macropa-derived PSMA inhibitors previously published by our group was performed in the MBq/nmol range.
Ergebnisse/Results:
Activity yields of 1.8 GBq lanthanum-133 (decay-corrected to EOB) were achieved, with corresponding lanthanum-135 impurities below 0.4 % and no other La radionuclides detected. The product was collected in diluted HCl, with ca. 80 % activity eluted in the second mL. Quantitative radiolabeling was achieved with ligand concentrations down to the µM range.
Schlussfolgerungen/Conclusions:
Lanthanum-133 with high radionuclidic purity was produced for the first time. Considering future medical demands, the scale up to radioactivity amounts that are needed for clinical application purposes could be achieved by increasing the target mass, beam current and irradiation time.