High yield cyclotron production of a novel 133/135La theranostic pair for nuclear medicine

This study reports the high-yield production of a novel ^133/135La theranostic pair at a 22 MeV proton beam energy as an attractive alternative to the recently introduced ^132/135La pair, demonstrating over an order of magnitude production increase of ^133/135La (231 ± 8 MBq ¹³³La and 166 ± 5 MBq ¹³⁵La at End of Bombardment (EOB)) compared to 11.9 MeV production of ^132/135La (0.82 ± 0.06 MBq ¹³²La and 19.0 ± 1.2 MBq ¹³⁵La) for 500 µA·min irradiations. A new sealed solid cyclotron target is introduced, which is fast to assemble, easy to handle, storable, and contains reusable components. Radiolabeling with macrocyclic chelators DOTA and macropa achieved full incorporation, with respective apparent ¹³³La molar activites of 33 ± 5 GBq/µmol and 30 ± 4 GBq/µmol. PET centers with access to a 22 MeV capable cyclotron could produce clinically-relevant doses of ^133/135La, via ^natBa irradiation, as a standalone theranostic agent for PET imaging and Auger electron therapy. With lower positron energies and less energetic and abundant gamma rays than ⁶⁸Ga, ⁴⁴Sc and ¹³²La, ¹³³La appears to be an attractive radiometal candidate for PET applications requiring a higher scanning resolution, a relatively long isotopic half-life, ease of handling, and a low patient dose.