Production of Lanthanum-133 via the134Ba(p,2n)133La Nuclear Reaction with High Radionuclide Purity for Theranostic Purposes

Aim/Introduction: Actinium-225 has gained great importance in Targeted Alpha Therapy (TAT) due to its suitable physical and chemical properties. In past years, studies using 225Ac-PSMA-617 have shown promising results [1], however, the macropa chelator has proven more beneficial properties regarding labelling and stability in vivo as compared with DOTA. While 68Ga has been used for DOTA-based radioconjugates, the macropa chelator lacks an imaging radionuclide counterpart. For this purpose, the β+-emitter 133La is an attractive candidate due to its physical properties and similar to 225Ac coordination chemistry. Following our recent publication [2], further optimization of the production of 133La with high radionuclidic purity (RNP) for theranostic purposes is presented. Materials and Methods: Lanthanum-133 was produced via the 134Ba(p,2n)133La nuclear reaction. Proton irradiation (19 MeV, 35 µA, 30 min) was performed using the HZDR TR-FLEX (ACSI) cyclotron on silver discs filled with 25 mg of [134Ba]BaCO3 capped with a 25 µm aluminum foil. The solid target was opened and the powder dissolved in 2 mL of 1 M HNO3. A one-step separation was carried out with a branched DGA resin cartridge after testing other resins. The 134Ba-containing fractions were collected and recycled through [134Ba]BaCO3 precipitation. Test radiolabelling of macropa-derived PSMA conjugates previously published by our group was performed in the MBq/nmol range [3]. Results: Lanthanum-133 yields of ca. 1.8 GBq for the described targets were reached at end of bombardment (EOB), accounting for about 65 % of the theoretical yield. After radiochemical separation, 1.2 GBq 133La were collected in 1 mL of 0.05 M HCl ready to label, with a RNP over 99.5 %. Further studies showed no detriment of the RNP by 21 MeV proton irradiation, thus being feasible irradiation of larger targets (prior thermal studies). Furthermore, quantitative radiolabeling was achieved with ligand concentrations down to 300 MBq/nmol. Conclusion: Lanthanum-133 of high RNP 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 irradiation time. Alternatively, irradiation with higher currents or of thicker targets could also lead to higher activities. Based on these results, our group will attempt to establish a diagnostic platform for 225Ac-TAT based on 133La-macropa radioconjugates instead of the conventional 68Ga-DOTA application. References: [1] Kratochwil et al., J. Nucl. Med. 2016, 57, 1941-1944 [2] Brühlmann et al., Pharmaceuticals 2022, 15, 1167. [3] Reissig et al., Cancers 2021, 13, 1974.