In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-111 monoclonal antibody metabolism

✍ Scribed by Yoshiko Kimura; Takashi Fujii; Kaori Ochi; Akihisa Akamune; Ken Hamamoto

• Book ID: 104653952
• Publisher: Springer
• Year: 1992
• Tongue: English
• Weight: 968 KB
• Volume: 19
• Category: Article
• ISSN: 0340-6997
• DOI: 10.1007/bf00182816

✦ Synopsis

The effects of diethylene triamine penta-acetic acid (DTPA) on indium-Ill monoclonal antibody (MoAb) metabolism were examined. Sequential analysis of mIn-MoAb incubated in serum at 37°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 rain to this fraction. It also decreased 111In uptake by isolated rat heptocytes but did not remove rain incorporated in hepatocytes. The daily in vivo administration of DTPA (0.5-2.0 rag/mouse daily) to athymic mice after mIn-MoAb injection significantly reduced the lUIn 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 UlIn released from the DTPA-MoAb conjugate in serum binds to molecules of 70-90 kDa and that DTPA decreases the rain uptake in this fraction, which induces a decrease of UlIn accumulation in normal tissues.