TY - JOUR T1 - First in vivo and phantom imaging of cyclotron produced <sup>133</sup>La as a theranostic radionuclide for <sup>225</sup>Ac and <sup>135</sup>La JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.262459 SP - jnumed.121.262459 AU - Bryce Nelson AU - Simon Ferguson AU - Melinda Wuest AU - John Wilson AU - John Duke AU - Susan Richter AU - Hans-Sonke Jans AU - Jan Andersson AU - Freimut Juengling AU - Frank Wuest Y1 - 2021/08/01 UR - http://jnm.snmjournals.org/content/early/2021/08/12/jnumed.121.262459.abstract N2 - Theranostic isotope pairs have gained recent clinical interest as they can be labeled to the same tracer and applied for diagnostic and therapeutic purposes. The goals of this study were to A) investigate cyclotron production of clinically relevant 133La activities using natural and isotopically enriched barium target material, B) compare fundamental positron emission tomography (PET) phantom imaging characteristics of 133La with common PET radionuclides, and C) demonstrate in vivo preclinical PET tumor imaging using 133La-PSMA-I&amp;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 NEPTIS Mosaic-LC performed Ba/La separation. DOTA, PSMA-I&amp;T, and macropa were radiolabeled with 133La. Derenzo and National Electrical Manufacturers Association (NEMA) 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&amp;T in LNCaP tumor-bearing mice. Results: Proton irradiations for 100 µA·min at 23.3 MeV yielded 214 ± 7 MBq 133La and 28 ± 1 MBq 135La using 135BaCO3, 59 ± 2 MBq 133La and 35 ± 1 MBq 135La using natBaCO3 and 81 ± 3 MBq 133La and 48 ± 1 MBq 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%. NEMA and Derenzo phantom imaging demonstrated 133La PET spatial resolution, and scanner recovery coefficient were superior compared to 68Ga, 132La, and comparable to 89Zr. The apparent molar activity was 130 ± 15 GBq/μmol with DOTA, 73 ± 18 GBq/μmol with PSMA-I&amp;T, and 206 ± 31 GBq/μmol with macropa. Preclinical PET imaging with 133La-PSMA-I&amp;T provided high-resolution tumor visualization with a SUV60min of 0.97 ± 0.17. Conclusion: With high-yield 133La cyclotron production, recovery of BaCO3 target material, and superior fundamental imaging characteristics compared to 68Ga and 132La, 133La represents a promising radiometal candidate to provide high-resolution PET imaging as a PET/alpha therapy theranostic pair with 225Ac, or a PET/Auger electron therapy theranostic pair with 135La. ER -