EFFECT OF CYCLOPHOSPHAMIDE ON THE BINDING OF (TCO4-)-TC-99M AND TC-99M-MDP TO BLOOD-CELLS AND PLASMA-PROTEINS

Since the introduction of technetium-99m (Tc-99m) and its rapid accept ance as a tool in nuclear medicine, very little information is availab le about its biological action as Tc-99m-radiopharmaceuticals. We have determined if cyclophosphamide, an alkylating agent, used in oncology as a chemotherapeutic drug, modifies the binding of (TcO4-)-Tc-99m an d Tc-99m-MDP (Tc-99m-methylenediphosphonic 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 pl asma and blood cells were separated. Cyclophosphamide (50 mu g) was in jected iv 1 h before the radiopharmaceuticals. Samples of plasma and b lood cells were also precipitated with 5% trichloroacetic acid and sol uble and insoluble fractions were isolated. The following results were obtained: 1) cyclophosphamide did not alter (0.25 to 8 h) percent rad ioactivity of (TcO4-)-Tc-99m in plasma or blood cells but increased th e binding of Tc-99m-MDP to blood cells; 2) cyclophosphamide did not al ter (0.25 to 8 h) the binding of (TcO4-)-Tc-99m in insoluble fraction of plasma and decreased(1 to 4 h) percent radioactivity of Tc-99m-MDP in the insoluble fraction of plasma; 3) cyclophosphamide increased (0. 25 to 4 h) percent radioactivity of (TcO4-)-Tc-99m in the insoluble fr action of blood cells but did not alter the binding of Tc-99m-MDP. Cyc lophosphamide and/or its metabolites modified the effective half-life of these radiopharmaceuticals (to (TcO4-)-Tc-99m was increased 2.3 to 3.4 h and to Tc-99m-MDP was decreased 3.3 to 2.1 h) and possibly incre ased the permeability of blood cells to (TcO4-)-Tc-99m.