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 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. <b>Methods:</b>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. <b>Results:</b> 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. <b>Conclusion:</b> 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.

Topics & Concepts