Palladium-103 as a Theranostic Auger Electron Emitter: From Cyclotron Production to Preclinical SPECT Evaluation in Murine and Canine Models

Background/Objectives: Palladium-103 (103Pd) is an Auger electron-emitting radionuclide with nanometer-scale penetration ranges that result in highly localized energy deposition, making it well suited for molecularly targeted radionuclide therapy. However, efficient production, separation, and in vivo evaluation workflows remain limited. This study aimed to establish a scalable workflow for the production, separation, purification, radiolabeling, and preclinical assessment of 103Pd for theranostic applications. Methods: 103Pd was produced via the 103Rh(p,n)103Pd reaction. An upgraded dry-distillation radionuclide separation equipment (RSE) enabled high-efficiency separation from irradiated rhodium foils, while a cotton-assisted acid recovery process yielded purified 103Pd suitable for radiolabeling. Chelation with NOTA and DOTA-TATE was performed, and radiochemical purity was assessed using iTLC, SPE, and a C18 column. In vivo SPECT/CT imaging was conducted in NMRI Nu/Nu mice and in a canine model with spontaneous liver metastatic spread of insulinoma, injected with [103Pd]Pd-labeled compounds. Results: The upgraded RSE achieved separation efficiencies of 64–86% and overall recovery yields of 81–94%, outperforming conventional wet-chemistry methods. Radiolabeling produced stable complexes with >95% radiochemical purity. SPECT/CT imaging confirmed in vivo stability in mice. In the canine model, a slight reduction in tumor size and increased glucose levels were observed during 24 days post-systemic application of 520 MBq of 103Pd-DOTA-TATE radioactivity. Conclusions: This study establishes a complete and efficient radiochemical and preclinical pipeline for 103Pd, demonstrating its feasibility as a theranostic radionuclide. The combination of high-yield production, robust separation chemistry, and localized Auger-mediated energy deposition highlights 103Pd as a promising candidate for future targeted radionuclide therapy applications.