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.

F-block; In vivo PET generator; Lanthanide separation; PET imaging; Radiolabeling; Theranostic radionuclides.