The radioactive 103Pd and 109Pd palladium bipyridyl–bisphosphonate complexes for radionuclide therapy of bone metastatic tumor cells

Abstract

Two radioisotopes of palladium, ¹⁰³Pd and ¹⁰⁹Pd, are considered promising candidates for therapeutic applications because they emit Auger electrons, which are known for their effectiveness in targeting and destroying cancerous cells. We synthesized complexes of ¹⁰³Pd and ¹⁰⁹Pd with two bipyridyl and one alendronate molecule. The complexes demonstrated stability and a strong affinity for the surface of hydroxyapatite grains, the main mineral component of bones. Radioactive complexes show significantly higher cytotoxicity against human prostate (DU 145) and ovarian Her2 positive (SKOV-3) cancer cell lines compared to trastuzumab labeled with the Auger electron emitter ¹²⁵I and cisplatin. The biological studies showed that both ¹⁰³Pd, a pure Auger electron emitter, and ¹⁰⁹Pd, which emits both beta and Auger electrons, demonstrate high cytotoxicity. Furthermore, it was observed that in the tested complexes, ^109mAg, a decay product of ¹⁰⁹Pd, was released from the complex following the decay of ¹⁰⁹Pd. In contrast, ^103mRh, a decay product of ¹⁰³Pd, remained within the structure of the complex. The release of ^103mRh from the ¹⁰³Pd complex is inhibited by the presence of delocalized electrons in the aromatic bipyridyl ligand. The concept of using a ¹⁰⁹Pd/^109mAg and ¹⁰³Pd/^103mRh generator encourages further exploration of this treatment strategy.