Radiochemical and biological behaviour of 153Sm and 166Ho complexes anchored by a novel bis(methylphosphonate) tetraazamacrocycle

The novel bis(methylphosphonate) 2,2'-[4,10-bis(phosphonomethyl)- 1,4,7,10-tetraazacyclododecane-1,7-diyl] diacetic acid, trans-H(6)DO2A2P, has been synthesized and characterized by multinuclear NMR spectroscopy (H-1, C-13 and P-31). Sm-153 and Ho-166 complexes with trans-H(6)DO2A2P have been prepared in high yield using a 1 : 2 metal to ligand molar ratio at 70 degrees C, pH 8-9. These complexes are hydrophilic, negatively charged and stable in vitro under physiological solutions, up to 48 h. They present a low plasmatic protein binding and some in vitro hydroxyapatite adsorption, mainly for Ho-166-trans-DO2A2P. Both complexes are stable in vivo, have a fast tissue clearance from most organs and a rapid total excretion from whole animal body. Moderate bone uptake was also observed but the accumulated radioactivity rapidly decreases with time.