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

Abstract

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 135BaCO3natBaCO3, 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 mA•min at 23.3 MeV yielded 214 6 7 MBq of 133La and 28 6 1 MBq of 135La using 135BaCO3, 59 6 2 MBq of 133La and 35 6 1 MBq of 135La using natBaCO3, and 81 6 3 MBq of 133La and 48 6 1 MBq of 135La using natBa metal. At 11.9 MeV, 135La yields were 81 6 2 MBq, 6.8 6 0.4 MBq, and 9.9 6 0.5 MBq for 135BaCO3natBaCO3, and natBa metal. BaCO3 target material recovery was 95.4% 6 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 6 15 GBq/mmol with DOTA, 73 6 18 GBq/mmol with PSMA-I&T, and 206 6 31 GBq/mmol with macropa. Preclinical PET imaging with 133La-PSMA-I&T provided high-resolution tumor visualization with an SUV of 0.97 6 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/a-therapy theranostic pair with 225Ac or as a PET/Auger electron therapy theranostic pair with 135La.