Technetium-99m Pyrophosphate: Comparison of ED50 for Tetany and Acidosis with Acute LD500

Abstract : Two severe biochemical disturbances appear to explain the acute clinical manifestations of toxic doses of 99mTc pyrophosphate when administered as a single intravenous bolus. These are reduction in the serum concentration of both total and ionized calcium and metabolic acidosis. The electrocardiogram and chemical analysis revealed that the hypocalcemic effect occurs at a much lower dosage than for the LD50. Polyphosphate was found to be more toxic by the LD50 analysis than pyrophosphate. It is emphasized that the hypocalcemic toxic effects should be the determining factor in deciding what dose of 99mTc Sn- pyrophosphate should be administered for bone scanning. At the dose level employed (.32 mg/kg), the authors have a safety factor of 40 to 1 with regard to the first signs of hypocalcemia by electrocardiographic measurements (i.e., 2 mg/kg). On this basis an injection of no more than 1 mg/kg is recommended to maintain a safety factor of around 10 to 1.