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

Abstract

Abstract 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.