IN-VITRO EFFECT OF CYCLOPHOSPHAMIDE ON THE BINDING OF RADIOPHARMACEUTICALS ((TCO4-)-TC-99M, AND (TC)-T-99M-MDP) TO BLOOD-ELEMENTS

Sodium pertechnetate ((TcO4-)-Tc-99m) and many Tc-99m-products are the radiopharmaceuticals most frequently used in nuclear medicine. Using an in vitro model, we evaluated the effect of cyclophosphamide on perc ent radioactivity of (TcO4-)-Tc-99m and methylenediphosphonic acid (Tc -99m-MDP) bound to isolated blood elements. Blood samples were incubat ed with the two radiopharmaceuticals, plasma and blood cells were sepa rated and precipitated, and soluble and insoluble fractions were separ ated. To evaluate the effect of cyclophosphamide, blood was incubated with this drug 1 h prior to the addition of the radiopharmaceuticals. The fraction of (TcO4-)-Tc-99m radioactivity was slightly higher in pl asma (61.2 to 53.8%) than in blood cells (38.8 to 46.2%) up to 6 h and cyclophosphamide did not interfere with this distribution. The amount of Tc-99m-MDP radioactivity was higher in plasma (91.1 to 87.2%) than in blood cells (8.9 to 12.8%) up to 24 h and cyclophosphamide did not modify it. The binding of (TcO4-)-Tc-99m to the insoluble fraction of plasma (4.9 to 6.1%) was low and cyclophosphamide did not interfere w ith it up to 6 h, but a small blockade (9.8 to 4.8%) was observed at 2 4 h. From 3 h on, cyclophosphamide slightly inhibited (TcO4-)-Tc-99m b inding to blood cells (23.1 to 16.6%) and increased it at 24 h (31.2 t o 14.3%). Cyclophosphamide did not alter Tc-99m-MDP binding to the ins oluble fraction of blood cells and slightly decreased Tc-99m-MDP bindi ng to the insoluble fraction of plasma (29.8 to 23.6%) up to 6 h. The effect of cyclophosphamide was strongest at 24 h, with decreased radio activity binding to the insoluble fraction of plasma (47.6 to 27.0%) a nd blood cells (51.2 to 23.2%). The fact that cyclophosphamide can bin d to plasma proteins and/or cross the cell membrane explains in part t he results obtained. Studies using other chemotherapeutic drugs may le ad to the development of an in vitro model for the evaluation of drug interaction with radiopharmaceutical substances.