Synthesis and biological evaluation of [(18)F]tetrafluoroborate: a PET imaging agent for thyroid disease and reporter gene imaging of the sodium/iodide symporter.

Abstract

PURPOSE:

The human sodium/iodide symporter (hNIS) is a well-established target in thyroid disease and reporter gene imaging using gamma emitters (123)I-iodide, (131)I-iodide and (99m)Tc-pertechnetate. However, no PET imaging agent is routinely available. The aim of this study was to prepare and evaluate (18)F-labelled tetrafluoroborate ([(18)F]TFB) for PET imaging of hNIS.

METHODS:

[(18)F]TFB was prepared by isotopic exchange of BF (4) (-) with [(18)F]fluoride in hot hydrochloric acid and purified using an alumina column. Its identity, purity and stability in serum were determined by HPLC, thin-layer chromatography (TLC) and mass spectrometry. Its interaction with NIS was assessed in vitro using FRTL-5 rat thyroid cells, with and without stimulation by thyroid-stimulating hormone (TSH), in the presence and absence of perchlorate. Biodistribution and PET imaging studies were performed using BALB/c mice, with and without perchlorate inhibition.

RESULTS:

[(18)F]TFB was readily prepared with specific activity of 10 GBq/mg. It showed rapid accumulation in FRTL-5 cells that was stimulated by TSH and inhibited by perchlorate, and rapid specific accumulation in vivo in thyroid (SUV = 72 after 1 h) and stomach that was inhibited 95% by perchlorate.

CONCLUSION:

[(18)F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans.

• Authors: Maite Jauregui-Osoro, Kavitha Sunassee, Amanda J Weeks, David J Berry, Rowena L Paul, Marcel Cleij, Jasvinder Paul Banga, Michael J O'Doherty, Paul K Marsden, Susan E M Clarke, James R Ballinger, Istvan Szanda, Sheue-Yann Cheng, Philip J Blower
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 37 Issue 11 Pg. 2108-16 (Nov 2010) ISSN: 1619-7089 [Electronic] Germany
• PMID: 20577737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Borates
• Boric Acids
• Fluorine Radioisotopes
• Symporters
• sodium-iodide symporter
• fluoroboric acid

Topics

• Animals
• Borates
• Boric Acids (chemical synthesis, metabolism, pharmacokinetics)
• Cell Line
• Drug Stability
• Female
• Fluorine Radioisotopes
• Genes, Reporter
• Humans
• Male
• Mice
• Molecular Imaging (methods)
• Positron-Emission Tomography (methods)
• Rats
• Symporters (genetics, metabolism)
• Thyroid Diseases (diagnostic imaging, metabolism)
• Thyroid Gland (cytology, metabolism)