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


CONCLUSIONS
[(18)F]TFB is an easily prepared PET imaging agent for rodent NIS and should be evaluated for hNIS PET imaging in humans.
Jauregui-Osoro
Maite
M
King's College London, St Thomas' Hospital, London, SE1 7EH, UK. Maite.Jauregui-Osoro@kcl.ac.uk
Sunassee
Kavitha
K
Weeks
Amanda J
AJ
Berry
David J
DJ
Paul
Rowena L
RL
Cleij
Marcel
M
Banga
Jasvinder Paul
JP
O'Doherty
Michael J
MJ
Marsden
Paul K
PK
Clarke
Susan E M
SE
Ballinger
James R
JR
Szanda
Istvan
I
Cheng
Sheue-Yann
SY
Blower
Philip J
PJ
D000818:Animals; D001881:Borates; D001888:Boric Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D002460:Cell Line; D004355:Drug Stability; D005260:Female; D005462:Fluorine Radioisotopes; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D013959:Thyroid Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
D001881:Borates; D001888:Boric Acids; D005462:Fluorine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C098759:fluoroboric acid