First In Vivo and Phantom Imaging of Cyclotron-Produced 133La as a Theranostic Radionuclide for 225Ac and 135La

Theranostic isotope pairs have gained recent clinical interest because they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to investigate cyclotron production of clinically relevant ¹³³La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of ¹³³La with those of common PET radionuclides, and demonstrate in vivo preclinical PET tumor imaging using ¹³³La-PSMA-I&T. Methods:¹³³La was produced on a 24-MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched ¹³⁵BaCO₃, ^natBaCO₃, and ^natBa metal. A synthesis unit performed barium/lanthanum separation. DOTA, PSMA-I&T, and macropa were radiolabeled with ¹³³La. Derenzo and National Electrical Manufacturers Association phantom imaging was performed with ¹³³La, ¹³²La, and ⁸⁹Zr and compared with ¹⁸F, ⁶⁸Ga, ⁴⁴Sc, and ⁶⁴Cu. In vivo preclinical imaging was performed with ¹³³La-PSMA-I&T on LNCaP tumor-bearing mice. Results: Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq of ¹³³La and 28 ± 1 MBq of ¹³⁵La using ¹³⁵BaCO₃, 59 ± 2 MBq of ¹³³La and 35 ± 1 MBq of ¹³⁵La using ^natBaCO₃, and 81 ± 3 MBq of ¹³³La and 48 ± 1 MBq of ¹³⁵La using ^natBa metal. At 11.9 MeV, ¹³⁵La yields were 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for ¹³⁵BaCO₃, ^natBaCO₃, and ^natBa metal. BaCO₃ target material recovery was 95.4% ± 1.7%. National Electrical Manufacturers Association and Derenzo phantom imaging demonstrated that ¹³³La PET spatial resolution and scanner recovery coefficients were superior to those of ⁶⁸Ga and ¹³²La and comparable to those of ⁸⁹Zr. The apparent molar activity was 130 ± 15 GBq/µmol with DOTA, 73 ± 18 GBq/µmol with PSMA-I&T, and 206 ± 31 GBq/µmol with macropa. Preclinical PET imaging with ¹³³La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 ± 0.17 at 60 min. Conclusion: With high-yield ¹³³La cyclotron production, recovery of BaCO₃ target material, and fundamental imaging characteristics superior to those of ⁶⁸Ga and ¹³²La, ¹³³La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/α-therapy theranostic pair with ²²⁵Ac or as a PET/Auger electron therapy theranostic pair with ¹³⁵La.