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. We 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.