Studies of carcino‐fetal proteins. III. Development of a radioimmunoassay for α‐fetoprotein. Demonstration of α‐fetoprotein in serum of healthy human adults

A radioimmunoassay (RIA) for human α‐fetoprotein (α‐FP) was developed. The sensitivity threshold of the method is 250 picograms per ml, which means that it is 20,000‐40,000 times more sensitive than immunodiffusion, and covers completely the thousandfold concentration gap between the α‐FP levels in normal human serum and the level detectable by immunodiffusion. Evidence for the presence of α‐FP in serum of healthy human individuals is as follows: (I) Normal serum in 1:5 dilution inhibited the binding of labelled α‐FP by antibody. (2) The activity inhibiting in RIA could be removed from serum by prior treatment with anti‐α‐FP immunoadsorbent. (3) At low pH α‐FP could be eluted from immunoadsorbent that had been previously treated with serum. (4) After fractionation of normal human serum by electrofocusing the activity inhibiting in RIA was present in a fraction whose isoelectric point was that previously shown for fetal α‐FP. The α‐FP present in cancer is currently believed to be a product of an activated fetal gene which is suppressed at the adult stage. Our results show that this suppression is not complete in all cells. Measurement of α‐FP at the radioimmunoassay level is considered to be a contribution to the early diagnosis of cancer.