Effect of cyclophosphamide on the binding of 99mTcO4 and 99mTc-MDP to blood cells and plasma proteins

RESUMO

Since the introduction of technetium-99m (99mTc) and its rapid acceptance as a tool in nuclear medicine, very little information is available about is biological action as 99mTc-radiopharmaceuticals. We have determined if cyclophosphamide, an alkylating agent, used in oncology as a chemotherapeutic drug, modifies the binding of 99mTCO-4 and 99mTc-MDP (99mTc-metylenediphosphonic acid) to blood cells and to plasma proteins. The radiopharmaceuticals were injected intravenously (iv) into SW-55 mice (male and female, weight 25 g) and samples of plasma and blood cells were separated. Cyclophosphamide (50 µg) was injected iv 1 h before the radipharmaceuticals. Samples of plasma and blood cells were also precipitated with 5 per cent trichloroacetic acid and soluble and insoluble fractions were isolated. The following results were obtained 1) cyclophosphamide did not alter (0.25 to 8h) percent radioactivity of 99m TcO04 in plasma or blood cells but increased the binding of 99m Tc-MDP to blood cells; 2) cyclophosphamide did not alter (o.25 to 8h) 6the binding of 99m TcO-4 in insoluble fraction of plasma and decreasde (1 to 4h) percent radioactivity of 99mTc-MDP in the insoluble fraction of plasma; 3) cyclophosphamide increased (0.25 to 4h) percent radioactivity of 99mTcO-4 in the insoluble fraction of blood cells but did not alter the binding of 99m Tc-MDP. Cyclophosphamide and/ or its methabolities modified the effective half-life of these radiopharmaceuticals (to 99TcO-4 was increased 2.3 to 3.4h and to 99mTc-MDP was decreased 3.3 to 2.1 h) and possibly increased the permeability of blood cells to 99m TcO-4