- 作者：Collin J. Weber ; Susan M眉ller ; Susan A. Safley ; Kereen B. Gordon ; Praveen Amancha ; Francois Villinger ; Vernon M. Camp ; Malgorzata Lipowska ; Jyotirmay Sharma ; Cristina M眉ller ; Roger Schibli ; Philip S. Low ; Christopher P. Leamon ; Raghuveer K. Halkar
- 刊名：Surgery
- 出版年：December, 2013
- 年：2013
- 卷：154
- 期：6
- 页码：1385-1393
- 全文大小：1659 K
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伪 and FR尾 was measured with the Illumina Human HT-12 Expression Bead聽Chips and verified by quantitative reverse-transcription polymerase chain reaction. Folate incorporation by PT cells versus normal thyroid cells was determined by incubation with 99mTechnetium (99mTc)(CO)3-folate and 99mTc-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伪 gene was expressed in all PTs analyzed, and the FR尾 gene was expressed by most. Uptake of 99mTc(CO)3-folate was increased in PT cells versus thyroid cells. There was dose-dependent uptake of 99mTc-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 99mTc-folate holds potential for localization of PT tumors preoperatively and their treatment.