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- Title
[F]tetrafluoroborate as a PET tracer for the sodium/iodide symporter: the importance of specific activity.
- Authors
Khoshnevisan, Alex; Jauregui-Osoro, Maite; Shaw, Karen; Torres, Julia; Young, Jennifer; Ramakrishnan, Nisha; Jackson, Alex; Smith, Gareth; Gee, Antony; Blower, Philip
- Abstract
Background: [F]BF, the first 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 [F]BF with higher SA. Methods: A new radiosynthesis of [F]BF was developed, involving reaction of [F]F with boron trifluoride diethyl etherate under anhydrous conditions, guided by B and F NMR studies of equilibria involving BF and BF. The SA of the product was determined by ion chromatography. The IC of [F]BF as an inhibitor of [F]BF uptake was determined in vitro using HCT116-C19 human colon cancer cells expressing the human form of NIS (hNIS). The influence of [F]BF dose on biodistribution in vivo was evaluated in normal mice by nanoPET imaging and ex vivo tissue counting. Results: An IC 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 [F]BF 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: [F]BF 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 [F]BF at higher SA with sufficient yield and without need for unusually high starting activity of [F]fluoride, removing the risk of NIS saturation in vivo even in mice. Trial registration: .
- Subjects
SODIUM iodide; TETRAFLUOROBORATES; FLUOBORATES; BORON trifluoride; CANCER cells
- Publication
EJNMMI Research, 2016, Vol 6, Issue 1, p1
- ISSN
2191-219X
- Publication type
Article
- DOI
10.1186/s13550-016-0188-5