Production of 135La via the 136Ba(p,2n)135La reaction and its DNA-damaging properties as a low-energy Auger electron emitter.

135La is an Auger-electron-emitting radionuclide with promising potential for targeted endoradiotherapy. To date, 135La has been produced mainly via the 135Ba(p,n)135La reaction, with reported activities limited to the 1 GBq range. In this work, we produced 135La via the higher-cross-section 136Ba(p,2n)135La reaction using enriched targets, reaching activities of up to 4.6 GBq at end of bombardment - the highest activity amount reported to date. Two target geometries were investigated, a 90° solid target and a 30° slanted target with higher [136Ba]BaCO3 mass. Their saturation yields were compared to theoretical predictions based on TENDL-2025 cross sections. Radiochemical purification, performed via one-step chromatography, allowed recovery of over 85% of the 135La activity in 1 mL of 0.01 M HCl with a radionuclidic purity above 99.99% and molar activities of 1200-3000 GBq/μmol at end of purification. Test radiolabeling with the macropa chelator gave apparent molar activities of 200-300 GBq/μmol, comparable to previously reported values for 133La. Moreover, the [135La]La-macropa complex showed high in vitro stability tested in human serum being over 99% intact after 48 h. Finally, to the best of our knowledge, we present the first experimental assessment of 135La-induced DNA strand breaks in a cell-free plasmid model, providing initial experimental support for its potential as an Auger-electron therapeutic radionuclide. These results support the 136Ba(p,2n)135La route as a scalable and reliable production method to produce 135La for future (pre)clinical radiopharmacological applications.