Production and radiochemistry of the in vivo PET generator 140Nd/140Pr as an imaging surrogate for F-block therapeutic radionuclides

Theranostics, a combined approach of diagnostics and therapeutics, often employs F-block therapeutic radionuclides including 225Ac, 177Lu, and 161Tb. While there is a lack of F-block PET imaging radionuclides, the in vivo PET generator pair 140Nd/140Pr can act as a theranostic imaging counterpart to the F-block therapeutic radionuclides. In this study, we explored the production and separation of high purity 140Nd via the 141Pr(p,2n)140Nd reaction route. Monoisotopic 141Pr targets irradiated with 20 MeV protons for 10 min with 10 µA beam current yielded 21.45 ± 0.82 MBq (580 ± 22 µCi) of 140Nd. A two-step separation method was developed for the purification of 140Nd from the 141Pr target material. Recoveries of 27.4 ± 2.1% 140Nd were obtained upon separation with < 20 ppb of 141Pr target material in the final product. Radiolabeling of Macropa and DOTA chelators with 140Nd resulted in [140Nd]Nd-Macropa with a molar activity of 74.0 MBq/µmol (2.0 mCi/µmol) and [140Nd]Nd-DOTA with a molar activity of 70.3 MBq/µmol (1.9 mCi/µmol). An imaging study with a phantom indicated the PET spatial resolution of 140Nd/140Pr was distinguishable down to 2.4 mm. This study sets the stage for the 140Nd/140Pr in vivo PET generator to be explored in radiopharmaceutical applications.