Evaluation of [F-18]-tetrafluoroborate as a potential PET imaging agent for the human sodium/iodide symporter in a new colon carcinoma cell line, HCT116, expressing hNIS

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Abstract

Purpose: 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, [F-18]-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 [Re-188]-perrhenate, [Tc-99m]-pertechnetate and [F-18]-tetrafluoroborate was evaluated with and without perchlorate inhibition using an automated radioimmune assay system, LigandTracer. The affinity of [F-18]-tetrafluoroborate for hNIS, and its half-maximal inhibitory concentration (IC50) for the inhibition of [Tc-99m]-pertechnetate transport were determined from the plateau accumulation of [F-18]-tetrafluoroborate and [Tc-99m]-pertechnetate, respectively, as a function of tetrafluoroborate concentration. Results: [F-18]-tetrafluoroborate accumulated effectively in both FRTL5 and HCT116-C19 cells. The accumulation in HCT116-C19 cells (plateau accumulation 31%) was comparable to that of [Re-188]-perrhenate (41%) and [Tc-99m]-pertechnetate (46%). Its affinity for hNIS and half-maximal inhibitory concentration (IC50) for the inhibition of pertechnetate uptake was approximately micromolar. Conclusion: We have produced a human colon cell line with a stable constitutive expression of functional hNIS (HCT116-hNIS-C19). [F-18]-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.
Original languageEnglish
Pages (from-to)98-105
Number of pages8
JournalNuclear Medicine Communications
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Animals
  • Biological Transport
  • Boric Acids
  • Borohydrides
  • Cloning, Molecular
  • Colonic Neoplasms
  • DNA, Complementary
  • Fluorine Radioisotopes
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Kinetics
  • Positron-Emission Tomography
  • Radioactivity
  • Rats
  • Rhenium
  • Sodium Pertechnetate Tc 99m
  • Symporters
  • Transfection

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