DEVELOPMENT OF A SENSITIVE 2-SITE IMMUNORADIOMETRIC ASSAY FOR PARATHYROID HORMONE-RELATED PEPTIDE - EVIDENCE FOR ELEVATED LEVELS IN PLASMA FROM PATIENTS WITH ADULT T-CELL LEUKEMIA LYMPHOMA AND B-CELL LYMPHOMA/

We have developed a sensitive immunoradiometric assay for PTH-related peptide (PTHrP) using a monoclonal antibody against PTHrP(1-34) and a polyclonal antibody against PTHrP(50-83), with recombinant human PTHrP (1-87) as the standard. The detection limit of the immunoradiometric a ssay was 0.5 pmol/L, and plasma PTHrP(1-87) concentrations in 110 heal thy subjects were 0.8 +/- 0.01 pmol/L, with the upper limit of the nor mal range being 1.1 pmol/L. Increased circulating PTHrP(1-87) concentr ations were demonstrated in all 46 cancer patients with hypercalcemia, but not in patients with primary hyperparathyroidism, chronic renal f ailure, or hypoparathyroidism. Normalization of serum calcium levels a fter resection of tumors was shown to correlate well with that of plas ma PTHrP(1-87) concentrations in 2 cancer patients. High circulating P THrP(1-87) levels were also demonstrated in 12 out of 13 hypercalcemic patients with adult T-cell leukemia/lymphoma and in 7 out of 8 hyperc alcemic patients with non-Hodgkin's lymphoma especially of B-cell type . These results suggest that PTHrP is a major humoral factor responsib le for the hypercalcemia frequently associated with adult T-cell leuke mia/lymphoma and also with B-cell lymphoma.