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

摘要

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 Dy-166/Ho-166 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 degrees 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 Dy-166/Ho-166-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 degrees C. Importantly, this is the first study of the use of the MOF concept to provide a highly-stable organometallic compound containing Dy-166/Ho-166 in vivo generator for bone marrow ablation.