Improved ¹⁴⁰Nd Production for the ¹⁴⁰Nd/¹⁴⁰Pr In Vivo Generator through Target Recycling and Radiochemical...

Theranostic strategies that utilize f-block therapeutic radionuclides, including ¹⁶¹Tb, ¹⁷⁷Lu, ²²⁵Ac, and ²²⁷Th, suffer from a shortage of positron emission tomography (PET) imaging counterparts in the same chemical space and often rely on ⁶⁸Ga as a surrogate. The ¹⁴⁰Nd/¹⁴⁰Pr in vivo PET generator, which belongs to the f-block, may address this issue and can be produced via the ¹⁴¹Pr-(p,2n)¹⁴⁰Nd production route by using medium-energy cyclotrons. However, impurities in the target material, including stable Nd, and the inherent difficulty of adjacent lanthanide separations limit the achievable radionuclidic and chemical purity of ¹⁴⁰Nd. In this work, we address these challenges through the purification and recycling of praseodymium target material and optimization of Nd/Pr separation. The resulting purified ¹⁴⁰Nd was evaluated using DOTA and Macropa chelators via radiolabeling and in vitro stability studies. A target material purification and recycling method was developed for the monoisotopic ¹⁴¹Pr starting material to remove stable Nd impurities, yielding 90.3 ± 4.7% (n = 3) recovery. The purified ¹⁴¹Pr was isolated as Pr₆O₁₁ and irradiated with 24 MeV protons (20.07 MeV at the target surface) at 20 μA for 4 h, which produced 1417.0 ± 83.4 MBq (38.3 ± 2.2 mCi) of ¹⁴⁰Nd at the end of bombardment (EOB). The produced ¹⁴⁰Nd was purified through an optimized DGA normal method to recover 71.6 ± 6.3% pure ¹⁴⁰Nd. The amount of stable Nd reduced progressively in each target purification cycle from >340 ppm without purification to <250 ppb after three cycles, while other measured metallic impurities were below 30 ppb. This improvement in target purity was reflected in the direct increase of apparent molar activity (AMA), when purified ¹⁴⁰Nd was evaluated with DOTA and Macropa chelators. AMA of [¹⁴⁰Nd]-Nd-DOTA and [¹⁴⁰Nd]-Nd-Macropa increased from 70.3 MBq/μmol (1.9 mCi/μmol) and 74 MBq/μmol (2.0 mCi/μmol) to 8025.3 MBq/μmol (216.9 mCi/μmol) and 8473.0 MBq/μmol (229.0 mCi/μmol), respectively, after the third target purification cycle. Further evaluation of chelator-labeled ¹⁴⁰Nd showed that [¹⁴⁰Nd]-Nd-DOTA was stable in phosphate-buffered saline (PBS), saline, human serum, and mouse serum, whereas [¹⁴⁰Nd]-Nd-Macropa was stable in all except human serum. This work established a practical methodological advance for the production of ¹⁴⁰Nd/¹⁴⁰Pr in vivo PET generators, combining optimized target recycling and radiochemical separation to enable scaled-up and high-molar activity ¹⁴⁰Nd suitable for preclinical imaging. These advances support broader development of ¹⁴⁰Nd/¹⁴⁰Pr as a robust PET analogue, especially for f-block therapeutics.