[18F]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 sat...

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Bibliographic Details
Published in:EJNMMI research 2016-04, Vol.6 (1), p.34, Article 34
Main Authors: Khoshnevisan, Alex, Jauregui-Osoro, Maite, Shaw, Karen, Torres, Julia Baguña, Young, Jennifer D., Ramakrishnan, Nisha K., Jackson, Alex, Smith, Gareth E., Gee, Antony D., Blower, Philip J.
Format: Article
Language:English
Subjects:
Cardiac Imaging
Imaging
Medicine
Medicine & Public Health
Nuclear Medicine
Oncology
Original Research
Orthopedics
Radiology
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Summary: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 .
ISSN:2191-219X
2191-219X
DOI:10.1186/s13550-016-0188-5