Synthesis, purification, and in vitro stability of 211At- and 125I-labeled amidobisphosphonates

A method is described for preparing 211At- and radioiodinated amidobisphosphonates. The active esters N-succinimidyl 3-(tri-methylstannyl) benzoate (ATE) and N-succinimidyl 5-(tri-methylstannyl)-3-pyridinecarboxylate (SPC) were used as precursors. The isolated and purified radiolabeled intermediates were coupled to 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APB) in high yields ranging from 60% to 97%. The lipophilicity of the compounds was found to depend on the nature of the labeled template and the halogen. High in vitro stability in mouse, fetal calf, and human serum was documented by high performance liquid chromatography.