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

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.