First In Vivo and Phantom Imaging of Cyclotron-Produced (133)La as a Theranostic Radionuclide for (225)Ac and (135)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 (133)La activities using natural and isotopically enriched barium target material, compare fundamental PET phantom imaging characteristics of (133)La with those of common PET radionuclides, and demonstrate in vivo preclinical PET tumor imaging using (133)La-PSMA-I&T. Methods: (133)La was produced on a 24-MeV cyclotron using an aluminum–indium sealed target with 150–200 mg of isotopically enriched (135)BaCO(3), (nat)BaCO(3), and (nat)Ba metal. A synthesis unit performed barium/lanthanum separation. DOTA, PSMA-I&T, and macropa were radiolabeled with (133)La. Derenzo and National Electrical Manufacturers Association phantom imaging was performed with (133)La, (132)La, and (89)Zr and compared with (18)F, (68)Ga, (44)Sc, and (64)Cu. In vivo preclinical imaging was performed with (133)La-PSMA-I&T on LNCaP tumor–bearing mice. Results: Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq of (133)La and 28 ± 1 MBq of (135)La using (135)BaCO(3), 59 ± 2 MBq of (133)La and 35 ± 1 MBq of (135)La using (nat)BaCO(3), and 81 ± 3 MBq of (133)La and 48 ± 1 MBq of (135)La using (nat)Ba metal. At 11.9 MeV, (135)La yields were 81 ± 2 MBq, 6.8 ± 0.4 MBq, and 9.9 ± 0.5 MBq for (135)BaCO(3), (nat)BaCO(3), and (nat)Ba metal. BaCO(3) target material recovery was 95.4% ± 1.7%. National Electrical Manufacturers Association and Derenzo phantom imaging demonstrated that (133)La PET spatial resolution and scanner recovery coefficients were superior to those of (68)Ga and (132)La and comparable to those of (89)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 (133)La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 ± 0.17 at 60 min. Conclusion: With high-yield (133)La cyclotron production, recovery of BaCO(3) target material, and fundamental imaging characteristics superior to those of (68)Ga and (132)La, (133)La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/α-therapy theranostic pair with (225)Ac or as a PET/Auger electron therapy theranostic pair with (135)La.