Synthesis, characterization, and in vitro evaluation of a radio-metal organic framework composed of in vivo generator ¹⁶⁶Dy/¹⁶⁶Ho and DOTMP as a novel agent for bone marrow ablation

In this study, the MOF concept contributed to the preparation of a novel, bone-ablating agent composed of Cu(II) using the in vivo generator ¹⁶⁶Dy/¹⁶⁶Ho and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP). The product was characterized (IR, elemental analysis: CHN, ICM-MS, PIXE, DLS, XRD) and quality-controlled (radio-thin layer chromatography (RTLC)). The stability and in vitro hydroxyapatite binding was checked up to one week at 37 C in human serum. Radio-MOF crystals and colloidal radio-MOF particles were obtained by varying the synthesizing conditions (including pH and temperature), and they had similar IR patterns and similar elemental analysis results. The estimated chemical formula was [1Lu-1Cu-1Cl-1DOTMP] for both. The final product was synthesized at pH = 8 while stirring at room temperature using ¹⁶⁶Dy/¹⁶⁶Ho-nitrate, CuCl₂, and DOTMP (yield > 99%, RTLC). Dynamic light scattering (DLS) measurements showed particles in the size range of 60 to 100 nm for the resultant radio-MOF particles (RMP). In vitro binding experiments showed acceptable bone-seeking affinity of the prepared formula even after one week of storage in human serum at 37 C. Importantly, this is the first study of the use of the MOF concept to provide a highly-stable organometallic compound containing ¹⁶⁶Dy/¹⁶⁶Ho in vivo generator for bone marrow ablation.