Comparative evaluation of three diphosphonates: in vitro adsorption (C- 14 labeled) and in vivo osteogenic uptake...

We have investigated the in vitro adsorption of three C-14-labeled diphosphonates on calcium phosphate. The three are 1-hydroxy[1-14C]ethylidene diphosphonate (C-14 HEDP), [14C]methylenediphosphonate (C-14 MDP), and hydroxy[14C]methylenediphosphonate (C-14 HMDP). All three adsorbed significantly more, per mole of calcium, on amorphous calcium phosphate than on crystalline hydroxyapatite. Among the three diphosphonates, C-14 HMDP adsorbed--on both amorphous and crystalline calcium phosphate--to a greater degree than did the other two bone-seeking agents. Moreover, when HMDP was complexed with Sn(II) and Tc-99m, it produced a significantly higher uptake of Tc-99m, per mg of calcium, in an isolated in vivo site of osteogenesis. The mechanisms of adsorption are discussed relative to the hydroxyl group on the diphosphonate, to the solubility of the calcium salts to the diphosphonates, and to the form of the calcium phosphate. These studies form a working rationale for the clinically observed high contrast obtained with Tc-99m HMDP between normal bone and soft tissue, and between normal and abnormal bone.