Radioactive labeling of protein carboxyl groups on factor VIII: use of carbodiimides for nuclear medicine

Carbodiimides have been used to study macromolecular structure and to produce immunologically active antigens. The authors have used this method to label a labile coagulation protein, factor VIII, with ¹⁴C-glycine-ethyl-ester. No discernible chemical change, loss of biologic function in vitro, or alteration of the plasma disappearance of factor VIII resulted. The carbodiimide labeling method has potentially broad application because many biologic molecules contain carboxyl groups that are generally not critical to their chemical or immunologic character. This method can be used to incorporate short-lived positron emitters, such as ¹¹C and ¹³N, into biologic compounds, or to attach ligands to useful antibodies for subsequent chelation to radioactive metals, such as ¹¹¹In. Carbodiimides are especially useful for radionuclidic labeling of labile proteins because of the mild conditions, rapid reaction, and firmly attached label.