INVITRO AND INVIVO EFFECTS OF DIETHYLENE TRIAMINE PENTA-ACETIC ACID ON THE DISTRIBUTION OF IN-111 MONOCLONAL-ANTIBODY METABOLISM

The effects of diethylene triamine penta-acetic acid (DTPA) on indium-111 monoclonal antibody (MoAb) metabolism were examined. Sequential analysis of In-111-MoAb incubated in serum at 37-degrees-C by high performance liquid chromatography (HPLC) and electrophoresis revealed that the radioactivity gradually moved from the MoAb to a 70-90 Kda molecular weight fraction. DTPA inhibited the transchelation of In-111 to this fraction. It also decreased In-111 uptake by isolated rat heptocytes but did not remove In-111 incorporated in hepatocytes. The daily in vivo administration of DTPA (0.5-2.0 mg/mouse daily) to athymic mice after In-111-MoAb injection significantly reduced the In-111 uptake in the liver and kidney. The tumour uptake was decreased somewhat but not significantly. The serum radioactivity in the 70-90 kDa fraction was also decreased. Scintigraphic examination demonstrated a decreased liver uptake in the DTPA-treated group of mice. Our results show that In-111 released from the DTPA-MoAb conjugate in serum binds to molecules of 70-90 kDa and that DTPA decreases the In-111 uptake in this fraction, which induces a decrease of In-111 accumulation in normal tissues.