Preparation of a biologically stable and immunogenically competent astatinated protein

A two step process has been developed for forming non-labile At-protein bonds. A stable astatine compound, p-astatobenzoic acid, was first prepared via a diazonium salt intermediate, and this compound was then added to bovine serum albumin (BSA) by a condensation reaction between the carboxylic acid group and an amine function on the protein. The tissue distribution patterns of 211At at intervals following injection of p-astatobenzoic acid-BSA conjugate into the tail vein of mice were compared with those following injection of free 211At-, and of free p-astatobenzoic acid. There were significant differences in the organ distribution patterns. The highest 211At concentration was found in liver after injection of astatinated BSA. The results suggest that the astatinated protein is non-labile in vivo over a period of 20 h. Studies of immunodiffusion and haemagglutination indicated that the 211At-labelled BSA possessed the majority of the entigenic properties of unlabelled BSA. The specific activity required for immunosuppression by suicide destruction of host lymphocytes was calculated and shown to be readily attainable using these preparative techniques. (U.K.)