In vitro effect of cyclophosphamide on the binding of radiopharmaceuticals (99mTcO4 and 99mTc-MDP) to blood elements

Sodium pertechnetate (99mTcO4) and many99m Tc-products are the radiopharmaceuticals most frequently used in nuclear medicine. Using an in vitro model, we evaluated the effect of cyclophosphamide on per cent radioactivity of 99mTcO4 and methylenedi-phosphonic acid (99mTc-MDP) bound toi isolated blood elements. Blood samples were incubated with the two radiopharmaceuticals, plasma and blood cells were separated and precipitated, and soluble and insoluble fractions were separated. To evaluate the effect of cyclophosphamide, blood was incubated with this drug 1h prior to the addition of the radiopharmaceuticals. The fraction of 99mTcO4 radioactivity was slightly higher in plasma (61.2 to 53.8 per cent) than in blood cells (38.8 to 46.2 per cent) up to 6 h and cyclophosphamide did not interfere with this distribution. The amount of 99mTc-mdp radioactivity was higher in plasma (91.1 to 87.2 per cent) than in blood cells 8.9 to 12.9 per cent) up to 24 h and cyclophosphamide did not modify it. The binding of 99mTcO4 to the insoluble fraction of plasma (4.9 to 6.1 per cent) was low and cyclophosphamide did not interfere with it up to 6h, but a small blockade (9.8 to 4.8 per cent) was observed at 24 h. From 3 h on, cyclophosphamide slightly inhibited 99mTcO4 binding to blood cells (23.1 to 16.6 per cent) and increased it at 24h (31.2 to 14.3 per cent). Cyclophosphamide did not alter 99mTc-MDP binding to the insoluble fraction of blood cells and slightly decreased 99mTc-MDP binding to the insoluble fraction of plasma (29.8 to 23.6 per cent) up to 6 h. The effect of cyclophosphamide was strongest at 24 h, with decreased radioactivity binding to the insoluble fraction of plasma (47.6 to 27.0 per cent) and blood cells (51.2 to 23.2 per cent). The fact that cyclophosphamide can bind to plasma proteins and/or cross the cell membrne explains in part the results obtained. Studies using other chemotherapeutic drugs may lead to the development of an in vitro model for the evaluation of drug interaction with radiopharmaceutical substances

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

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