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

TY - JOUR

T1 - 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

AU - Weeks, Amanda

AU - Jauregui-Osoro, Maite

AU - Cleij, Marcel

AU - Blower, Julia E

AU - Ballinger, James R

AU - Blower, Philip J

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

KW - Animals

KW - Biological Transport

KW - Boric Acids

KW - Borohydrides

KW - Cloning, Molecular

KW - Colonic Neoplasms

KW - DNA, Complementary

KW - Fluorine Radioisotopes

KW - Gene Expression Regulation, Neoplastic

KW - HCT116 Cells

KW - Humans

KW - Kinetics

KW - Positron-Emission Tomography

KW - Radioactivity

KW - Rats

KW - Rhenium

KW - Sodium Pertechnetate Tc 99m

KW - Symporters

KW - Transfection

U2 - 10.1097/MNM.0b013e3283419540

DO - 10.1097/MNM.0b013e3283419540

M3 - Article

C2 - 21085047

SN - 1473-5628

VL - 32

SP - 98

EP - 105

JO - Nuclear Medicine Communications

JF - Nuclear Medicine Communications

IS - 2

ER -