title: Evaluation of [18F]-tetrafluoroborate as a potential PET imaging agent for the human sodium/iodide symporter in a new colon carcinoma cell line, HCT116, expressing hNIS.
abstract: OBJECTIVE
  Accumulation of iodide and other substrates via the human sodium/iodide symporter (hNIS) is fundamental to imaging and therapy of thyroid disease, hNIS reporter gene imaging and hNIS-mediated gene therapy. There is no readily available positron emission tomography (PET) tracer for hNIS. Our aim was to develop a colon carcinoma cell line stably expressing hNIS, and use it to evaluate a novel hNIS PET tracer, [18F]-tetrafluoroborate.
  
  
  METHODS
  Colon carcinoma cell line, HCT116, was stably transfected with hNIS, thus producing a cell line, HCT116-C19, with high hNIS expression. A Fisher rat thyroid cell line, FRTL5, which expresses rat sodium/iodide symporter when stimulated with thyroid-stimulating hormone, was used for comparison. Accumulation of [188Re]-perrhenate, [99mTc]-pertechnetate and [18F]-tetrafluoroborate was evaluated with and without perchlorate inhibition using an automated radioimmune assay system, LigandTracer. The affinity of [18F]-tetrafluoroborate for hNIS, and its half-maximal inhibitory concentration (IC50) for the inhibition of [99mTc]-pertechnetate transport were determined from the plateau accumulation of [18F]-tetrafluoroborate and [99mTc]-pertechnetate, respectively, as a function of tetrafluoroborate concentration.
  
  
  RESULTS
  [18F]-tetrafluoroborate accumulated effectively in both FRTL5 and HCT116-C19 cells. The accumulation in HCT116-C19 cells (plateau accumulation 31%) was comparable to that of [188Re]-perrhenate (41%) and [99mTc]-pertechnetate (46%). Its affinity for hNIS and half-maximal inhibitory concentration (IC50) for the inhibition of pertechnetate uptake was approximately micromolar.
  
  
  CONCLUSIONS
  We have produced a human colon cell line with a stable constitutive expression of functional hNIS (HCT116-hNIS-C19). [18F]-tetrafluoroborate accumulates in cells expressing hNIS or rat sodium/iodide symporter and is a potential PET imaging agent in thyroid disease and hNIS reporter gene imaging.
authors.affiliation: Division of Imaging Sciences, King's College London, St Thomas' Hospital, London, UK.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Weeks
authors.forename: Maite
authors.initials: M
authors.lastname: Jauregui-Osoro
authors.forename: Marcel
authors.initials: M
authors.lastname: Cleij
authors.forename: Julia E
authors.initials: JE
authors.lastname: Blower
authors.forename: James R
authors.initials: JR
authors.lastname: Ballinger
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Blower
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001881:Borates; D001888:Boric Acids / Q000378:metabolism; D001894:Borohydrides / Q000494:pharmacology; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D005462:Fluorine Radioisotopes; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007700:Kinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011851:Radioactivity; D051381:Rats; D012211:Rhenium / Q000378:metabolism; D013670:Sodium Pertechnetate Tc 99m / Q000378:metabolism; D027981:Symporters / Q000235:genetics*; D014162:Transfection; D000099209:Sodium-Iodide Symporters
chemical_list: D001881:Borates; D001888:Boric Acids; D001894:Borohydrides; D018076:DNA, Complementary; D005462:Fluorine Radioisotopes; D012211:Rhenium; D013670:Sodium Pertechnetate Tc 99m; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C015428:perrhenate; C025364:sodium borohydride; C098759:fluoroboric acid