Radioimmunoassay for the detection of prohormone/propeptide enzymes and for diagnosis and monitoring of enzyme levels.
- Radioimmunoassay can be applied as a diagnostic for a number of clinical pathologies including hormone secreting cancers such as neuroendocrine tumors; gastrinomas; insulinomas; and familial hyperinsulinemias; and other related endocrinopathologies.
- Antibodies developed for use in this assay are highly selective and very specific, detecting serum propeptide/prohormone convertase levels as low as 5 picograms.
An estimated 21 million Americans have diabetes and 11,000 to 12,000 new neuroendocrine tumors are diagnosed each year in the U.S. Active forms of peptides are often first synthesized as larger inactive precursors. Such precursors are enzymatically cleaved to form biologically active molecules. Endoproteases or Prohormone/Propeptide Convertases (PCs) play significant roles in processing hormones. Two such PCs, PC1 and PC2, are predominately expressed within endocrine and neuroendocrine cells and tissues. Hypersecretion of gastric acids and insulin is associated with neuroendocrine tumors such as gastrinomas and insulinomas, respectively. Since PCs are sequestered in secretory granules along with their prohormone substrates, hypersecretion of the hormone is accompanied by hypersecretion of the PCs. A radioimmunoassay (RIA) has been developed to detect human PC1 and PC2. The antibodies were generated against the amino-terminus of the human PC1 and PC2 catalytic domains and fully cross react with the mouse PC1 and PC2 convertases. Serum samples tested detected PC levels as low as 10 picograms for PC1 and 5 picograms for PC2. Clinical uses for this assay include monitoring PC1 and PC2 processing defects occurring in cases of familia hyperproinsuliniemia, hyperproglucagonemia, non-insulin dependent (Type II) diabetes, increased levels of prohormone expression in cases of pancreatic cancer, and defective prohormone processing as in polyendocrine disease. Basic research uses include the expression, release, and cleavage specificity of PC1 and PC2.
Antibodies have been developed and utilized in a radioimmunoassay to detect serum levels of PC1 and PC2.