Technetium/sup 99/-methylene dihosphonate; a superior agent for skeletal imaging: comparison with other technetium complexes

Methylene diphosphonate (MDP) was formulated as a complex of /sup 99m/Tc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with /sup 95m/Tc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of /sup 95m/Tc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of /sup 99m/Tc-MDP was similar to that of 18F and significantly faster than that of /sup 99m/Tc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2 to 3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four /sup 99m/Tc complexes proved 0000sfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3 to 4 hr after injection was usually needed for /sup 99m/Tc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparative radiation dose estimates were made based on the available biologic distribution data for these /sup 99m/Tc skeletal-localizing agents. (U.S.)