Improved procedures for production and purification of ¹³⁵La from enriched [¹³⁵Ba]BaCO₃ on a 16.5 MeV cyclotron

Lanthanum-135 (¹³⁵La) is a favorable Auger electron emitter with a high Auger electron yield and low gamma emission, making it promising for Auger electron radiotherapy. However, successful application requires reliable and scalable ¹³⁵La production. Up to now, metallic natural barium (^natBa) is a commonly used target material, but this material is sensitive to moisture and oxidation. BaCO₃ has also been tested, due to its higher chemical stability. However, BaCO₃ has poor thermal conductivity, limiting the applicable current and making high yield production challenging. In this study, we pressed a mixture of enriched [¹³⁵Ba]BaCO₃ and fine aluminum (Al) powder to provide a stable target with improved thermal conductivity compared to pure BaCO₃. After 4 h of irradiation with a 16.5 MeV proton beam at 20 μA current, 1.62 ± 0.18 GBq was produced from a 200 mg [¹³⁵Ba]BaCO₃:Al (1:2, w/w) target. This corresponded to a saturation yield of 11.91 ± 1.31 GBq (or 596 ± 66 MBq/μA). A purification procedure involving initial precipitation, followed by a single composite column containing a layer of TK200 resin and a second layer of branched DGA resin was developed, with 97.1 ± 3.6 % decay corrected ¹³⁵La recovery. [¹³⁵La]LaCl₃ was obtained in an effective molar activity of 79.6 ± 25.3 MBq/nmol (DOTA titration), 104.0 ± 40.4 MBq/nmol (DTPA titration) and 186.5 ± 83.8 MBq/nmol (CHX-A″-DTPA titration), and a radionuclidic purity (RNP) of >99.9 % at end of purification, hereby demonstrating a purity suitable for radiopharmaceutical use.