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

• Published in: Nuclear medicine communications Vol. 32; no. 2; p. 98
• Main Authors: Weeks, Amanda J, Jauregui-Osoro, Maite, Cleij, Marcel, Blower, Julia E, Ballinger, James R, Blower, Philip J
• Format: Journal Article
• Language: English
• Published: England 01.02.2011
• Subjects: Animals; Biological Transport - drug effects; Borates; Boric Acids - metabolism; Borohydrides - pharmacology; Cloning, Molecular; Colonic Neoplasms - diagnostic imaging; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; DNA, Complementary - genetics; Fluorine Radioisotopes; Gene Expression Regulation, Neoplastic; HCT116 Cells; Humans; Kinetics; Positron-Emission Tomography - methods; Radioactivity; Rats; Rhenium - metabolism; Sodium Pertechnetate Tc 99m - metabolism; Symporters - genetics; Transfection
• ISSN: 1473-5628
• DOI: 10.1097/MNM.0b013e3283419540

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. 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. [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. 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.