Sensitive and specific assay for human chorionic gonadotropin (hCG) based on anti-peptide and anti-hCG monoclonal antibodies: construction and clinical implications.

We developed a highly sensitive and specific assay for hCG using monoclonal antibodies (Mabs) directed against a 37-amino acid synthetic polypeptide analogous to the carboxyl-terminus (CTP) of beta hCG. Five antibodies that varied by either their affinity for beta hCG or their specificity for epitopes on CTP were investigated. To measure hormone levels, we used as the radiolabeled indicator an alpha-subunit-reactive Mab. The monoclonal-immunoradiometric assay had a lower limit of sensitivity of 0.05 ng/ml. Serum levels of hCG or hCG-like material with CTP structure were measured in 229 healthy blood donors; 1.1% of healthy men and 4.6% of nonpregnant women younger than 50 yr had serum values varying between 0.05 and 0.23 ng/ml. Moreover, 6 to 7 healthy women older than 50 yr had detectable levels in the 0.05-0.20 ng/ml range. To study the disappearance rates in normal women, we followed serum hCG serum levels of 6 women who had previously received a single im injection of the hormone. These individuals failed to develop a pregnancy after in vitro fertilization; hCG declined from 0.5 to 0.05 ng/ml within 2 weeks. These results were in contrast to the findings in 12 patients with hCG-producing tumors. In 9 patients without any evidence of recurrent disease, hCG levels became undetectable within 5 months. However, 3 others had levels consistently above 0.05 but below 0.5 ng/ml. In 2 of these three patients, subsequent increasing hCG levels were associated with tumor recurrence. We conclude that this hCG assay based on both anti-peptide and anti-hCG Mabs may be useful in tumor monitoring.