Expression of functional folate receptors by human parathyroid cells

Background. Human pituitary adenomas express folate receptors (FR); therefore, we hypothesized that parathyroid (PT) tumors also might express FR, whereas normal human thyroids might not. The purpose of our study was to characterize the functionality of FRs on human PT tumors, with the goal of developing an imaging tool that would concentrate in PT more than in the thyroid. Methods. Human PTs and thyroids were evaluated for FR expression by immunohistochemistry. Expression of genes for FR alpha and FR beta was measured with the Illumina Human HT-12 Expression Bead Chips and verified by quantitative Averse-transcription polymerase chain reaction. Folate incorporation by PT cells versus normal thyroid cells was determined by incubation with (99m)Technetium (Tc-99m)(CO)(3)-folate and Tc-99m-Etarfolatide, and uptake was determined by gamma counting. Specific targeting of FRs was demonstrated by blocking with cold folate. A549 cells and Jurkat cells served as FR-negative controls, and KB cells and HeLa cells were FR-positive controls. Results. On immunohistochemistry and Western blotting, human PT cells expressed FRs, whereas human thyroid cells did not. The FR alpha gene was expressed in all PTs analyzed, and the FR beta gene was expressed by most. Uptake of Tc-99m(CO)(3)-folate was increased in PT cells versus thyroid cells. There was dose-dependent uptake of Tc-99m-etarfolatide, and uptake was inhibited by preincubation with cold folate, confirming FR-mediated binding. Conclusion. This is the first report of the expression and functionality of FRs on human PT cells. These findings suggest that Tc-99m-folate holds potential for localization of PT tumors preoperatively and their treatment.