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

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 La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of La with those of common PET radionuclides, and demonstrate in vivo preclinical PET tumor imaging using La-PSMA-I&T. La was produced on a 24-MeV cyclotron using an aluminum-indium sealed target with 150-200 mg of isotopically enriched BaCO, BaCO, and Ba metal. A synthesis unit performed barium/lanthanum separation. DOTA, PSMA-I&T, and macropa were radiolabeled with La. Derenzo and National Electrical Manufacturers Association phantom imaging was performed with La, La, and Zr and compared with F, Ga, Sc, and Cu. In vivo preclinical imaging was performed with La-PSMA-I&T on LNCaP tumor-bearing mice. Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq of La and 28 ± 1 MBq of La using BaCO, 59 ± 2 MBq of La and 35 ± 1 MBq of La using BaCO, and 81 ± 3 MBq of La and 48 ± 1 MBq of La using Ba metal. At 11.9 MeV, La yields were 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for BaCO, BaCO, and Ba metal. BaCO target material recovery was 95.4% ± 1.7%. National Electrical Manufacturers Association and Derenzo phantom imaging demonstrated that La PET spatial resolution and scanner recovery coefficients were superior to those of Ga and La and comparable to those of Zr. 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 La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 ± 0.17 at 60 min. With high-yield La cyclotron production, recovery of BaCO target material, and fundamental imaging characteristics superior to those of Ga and La, La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/α-therapy theranostic pair with Ac or as a PET/Auger electron therapy theranostic pair with La.