Effect of DTPA on biodistribution of 111In-labeled monoclonal antibody in tumor-bearing mice]

To reduce the high background liver radioactivity in immunoscintigraphy using 111In-labeled monoclonal antibody (In-MoAb), we investigated the effect of diethylenetriaminepentaacetic acid (DPTA) on the in vitro stability of In-MoAb in human serum and the biodistribution of In-MoAb in tumor-bearing mice. In-MoAb was incubated for four days in human serum at 37 degrees C (pH 7.4) in a humidified atmosphere at 5% CO2. The serum sample was analyzed by high performance liquid chromatography every day. Indium-111 gradually transferred from the conjugate to the fraction of transferrin. When DTPA was added to the serum, radioactivity in this fraction disappeared completely and moved to the fraction of DTPA. The daily administration of DTPA to the mice after injection of In-MoAb reduced radioactivity in the normal tissues, especially in the liver after the second day, and improved tumor to normal tissue ratios. Scintigraphic examination also revealed apparent decrease of the liver radioactivity in the mice administered DTPA. These results indicate that 111In dissociated from the conjugate is one of the causes of nonspecific accumulation in the liver and it is possible to decrease this accumulation by the daily administration of DTPA.