John D. Rodwell

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.

Murine cytomegalovirus inactivated by sodium periodate is innocuous and immunogenic in mice and protects them against death and infection

Sodium periodate (10 mM, 4 degrees C) inactivated murine cytomegalovirus (MCMV) very rapidly (loss of 2 to 3 log of viral infectivity per minute). Periodate-treated MCMV (PI-MCMV) was shown to be innocuous in mice, as determined by the inability of the virus to replicate. PI-MCMV induced a strong humoral immune response, with a high level of neutralizing antibodies. Mice immunized with PI-MCMV were protected against death and infection, when a lethal challenge with the virulent virus was administered 3 weeks after immunization and from death but not infection when virulent virus was administered at 3 months. Finally, no reactivation of potentially latent challenge virus (sublethal dose at 3 weeks) was observed in animals immunosuppressed at 6 months after immunization. Taken together, these results suggest that periodate could serve as an inactivating agent to prepare killed vaccines.