Site-specifically modified 111In labelled antibodies give low liver backgrounds and improved radioimmunoscintigraphy.
Site-specific modification of monoclonal antibodies at their oligosaccharide had previously been demonstrated to produce excellent 111In imaging in a xenograft model using a Brown Norway (BN) rat lymphoma and a rat anti-BN MHC monoclonal antibody [Lee C. et al. Fed. Proc. Abstr. 43 3014 (1984)]. These results are due, in part, to lack of liver uptake, so we wanted to evaluate the extent of hepatic uptake observed with different monoclonal antibodies in normal mice. Biodistribution data were obtained for four monoclonal antibodies by first modifying each antibody at its carbohydrate with a diethylenetriaminepentaacetic acid (DTPA) derivative. The antibodies were then labelled with 111In and injected into normal mice. Images were obtained 24 h post-injection, and at 48 h the mice were dissected and the tissue-to-blood (T:B) ratios determined. T:B ratios were approximately 1 (or less) for every organ evaluated, indicating minimal non-specific uptake into these organs. Data is also presented for the BN-rat system which shows excellent localization into the tumor xenograft and low non-specific organ uptake. These data indicate that modification of antibodies site-specifically at their oligosaccharide results in minimal non-specific uptake into non-target tissues and enhanced localization into the tumor target, and that this may represent a preferred method for production of 111In labelled antibodies.
D000818:Animals; D000911:Antibodies, Monoclonal; D005260:Female; D006801:Humans; D007204:Indium; D008099:Liver / Q000000981:diagnostic imaging*; D008223:Lymphoma / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011868:Radioisotopes; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D007204:Indium