[(18)F]tetrafluoroborate as a PET tracer for the sodium/iodide symporter: the importance of specific activity

BACKGROUND: [(18)F]BF(4)(−), the first (18)F-labelled PET imaging agent for the sodium/iodide symporter (NIS), was produced by isotopic exchange yielding a product with limited specific activity (SA, ca. 1 GBq/μmol) posing a risk of sub-optimal target-to-background ratios (TBR) in PET images due to saturation of NIS in vivo. We sought to quantify this risk and to develop a method of production of [(18)F]BF(4)(−) with higher SA. METHODS: A new radiosynthesis of [(18)F]BF(4)(−) was developed, involving reaction of [(18)F]F(−) with boron trifluoride diethyl etherate under anhydrous conditions, guided by (11)B and (19)F NMR studies of equilibria involving BF(4)(−) and BF(3). The SA of the product was determined by ion chromatography. The IC(50) of [(19)F]BF(4)(−) as an inhibitor of [(18)F]BF(4)(−) uptake was determined in vitro using HCT116-C19 human colon cancer cells expressing the human form of NIS (hNIS). The influence of [(19)F]BF(4)(−) dose on biodistribution in vivo was evaluated in normal mice by nanoPET imaging and ex vivo tissue counting. RESULTS: An IC(50) of 4.8 μΜ was found in vitro indicating a significant risk of in vivo NIS saturation at SA achieved by the isotopic exchange labelling method. In vivo thyroid and salivary gland uptake decreased significantly with [(19)F]BF(4)(−) doses above ca. 10 μg/kg. The new radiosynthesis gave high radiochemical purity (>99 %) and moderate yield (15 %) and improved SA (>5 GBq/μmol) from a starting activity of only 1.5 GBq. CONCLUSIONS: [(18)F]BF(4)(−) produced at previously reported levels of SA (1 GBq/μmol) can lead to reduced uptake in NIS-expressing tissues in mice. This is much less likely in humans. The synthetic approach described provides an alternative for production of [(18)F]BF(4)(−) at higher SA with sufficient yield and without need for unusually high starting activity of [(18)F]fluoride, removing the risk of NIS saturation in vivo even in mice. TRIAL REGISTRATION: ISRCTN75827286. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-016-0188-5) contains supplementary material, which is available to authorized users.