Fate of an antibody-ricin A chain conjugate administered to normal rats

The pharmacokinetics and catabolism of ricin A chain, a mouse monoclonal antibody (LICR-LOND-Fib 75) and a disulphide linked conjugate of the two have been studied following their intravenous administration to normal rats. Results indicate that the conjugate was removed from the circulation much more rapidly than the antibody but less quickly than the free ricin A chain. Disappearance of the conjugate from the circulation appeared to be biphasic with an early rapid initial phase followed by a much more rapidly than the antibody but less quickly than the free ricin A chain. Disappearance of the conjugate from the circulation appeared to be biphasic with an early rapid initial phase followed by a much slower phase. The fate of a conjugate with a 125I iodide label in the antibody component was compared with that of a conjugate similarly labelled but in the ricin A chain component. The results indicate that breakdown of the conjugate involves both cleavage of the disulphide linkage and complete catabolism of the whole conjugate molecule with the release of 125I iodide. Rapid cleavage of the disulphide bond in the vasculature does not appear to be responsible for the initial rapid disappearance of the conjugate from the circulation.