In vitro and in vivo effects of diethylene triamine penta-acetic acid on the distribution of indium-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 111In-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 111In to this fraction. It also decreased 111In uptake by isolated rat hepatocytes but did not remove 111In incorporated in hepatocytes. The daily in vivo administration of DTPA (0.5-2.0 mg/mouse daily) to athymic mice after 111In-MoAb injection significantly reduced the 111In 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 111In released from the DTPA-MoAb conjugate in serum binds to molecules of 70-90 kDa and that DTPA decreases the 111In uptake in this fraction, which induces a decrease of 111In accumulation in normal tissues.
Kimura
Y
Y
Department of Radiology, Ehime University School of Medicine, Japan.
Fujii
T
T
Ochi
K
K
Akamune
A
A
Hamamoto
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007205:Indium Radioisotopes; D007668:Kidney / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D004369:Pentetic Acid / Q000494:pharmacology*; D016719:Radioimmunodetection; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D007205:Indium Radioisotopes; D004369:Pentetic Acid