Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

Alpha particles show great promise for therapeutic applications due to their high rate of linear energy transfer over short path lengths. Radium-223 has excellent decay properties but, a major hurdle for its use is the development of a stable chelator for delivery to the tumor site. Work is underway testing polyoxopalladates, as a novel subclass of polyoxometalates (POMs), to complex barium and radium and establish the feasibility of their radiopharmaceutical use. Nonradioactive BaPd15 POMs were produced by the reported literature method and characterized by NMR, TLC, and HPLC. Radioactive [133Ba, 224Ra]BaPd15 POMs were prepared similarly with either [133Ba]BaCl2 or [224Ra]RaCl2 spiked into the solution prior to heating. Characterization was performed by NMR, RadioTLC, and HPLC. Chromatographic separations were tested using Dowex-50 and Sephadex G-15 to purify the POM product. Dialysis studies were carried out to determine the stability of the [133Ba]BaPd15. Incubation studies with rat serum were performed to explore their biological stability. The POMs were easily prepared in a one-pot reaction and characterized by 1H and 13C NMR. TLC and HPLC were performed to determine the percent of incorporated radionuclide. Cation exchange chromatography with Dowex 50-X8 removed free [133Ba]Ba2+ to non-detectable levels in the product. Size exclusion chromatography with Sephadex G-15 separated the BaPd15 product (eluted first) from the bulk excess of acetate buffer and phenylarsonic acid. Dialysis studies showed measurable quantities of 133Ba in solution after 1 hour and ~ 10% of the radionuclide had escaped after 24 hours. Serum studies indicated the POMs had affinity for serum proteins quickly upon contact with the serum. The results of this study demonstrate the development of radioactive [133Ba, 224Ra]BaPd15 POMs. Stability studies indicated that these POMs quickly began to decompose, significantly so after 24 hours. Additionally, incubation studies with rat serum demonstrated an affinity for serum proteins. For these reasons, these POMs are unsuitable for radiotherapeutic use.