title: Expression of functional folate receptors by human parathyroid cells.
abstract: 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 FRα and FRβ was measured with the Illumina Human HT-12 Expression Bead Chips and verified by quantitative reverse-transcription polymerase chain reaction. Folate incorporation by PT cells versus normal thyroid cells was determined by incubation with (99m)Technetium ((99m)Tc)(CO)3-folate and (99m)Tc-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 FRα gene was expressed in all PTs analyzed, and the FRβ gene was expressed by most. Uptake of (99m)Tc(CO)3-folate was increased in PT cells versus thyroid cells. There was dose-dependent uptake of (99m)Tc-etarfolatide, and uptake was inhibited by preincubation with cold folate, confirming FR-mediated binding.
  
  
  CONCLUSIONS
  This is the first report of the expression and functionality of FRs on human PT cells. These findings suggest that (99m)Tc-folate holds potential for localization of PT tumors preoperatively and their treatment.
authors.affiliation: Department of Surgery, Emory University, Atlanta, GA. Electronic address: cweber@emory.edu.
authors.forename: Collin J
authors.initials: CJ
authors.lastname: Weber
authors.forename: Susan
authors.initials: S
authors.lastname: Müller
authors.forename: Susan A
authors.initials: SA
authors.lastname: Safley
authors.forename: Kereen B
authors.initials: KB
authors.lastname: Gordon
authors.forename: Praveen
authors.initials: P
authors.lastname: Amancha
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Camp
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lipowska
authors.forename: Jyotirmay
authors.initials: J
authors.lastname: Sharma
authors.forename: Cristina
authors.initials: C
authors.lastname: Müller
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Leamon
authors.forename: Raghuveer K
authors.initials: RK
authors.lastname: Halkar
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D058975:Folate Receptor 1 / Q000235:genetics* / Q000378:metabolism*; D058976:Folate Receptor 2 / Q000235:genetics* / Q000378:metabolism*; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D007624:KB Cells; D015609:Organotechnetium Compounds / Q000378:metabolism; D010280:Parathyroid Glands / Q000000981:diagnostic imaging / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000378:metabolism; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: C548696:FOLR1 protein, human; D058975:Folate Receptor 1; D058976:Folate Receptor 2; D015609:Organotechnetium Compounds; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019275:Radiopharmaceuticals; D005492:Folic Acid