Rapid Uptake, Metabolism, and Elimination of Inhaled Sulfuryl Fluoride Fumigant by Rats

Mendrala, Alan L.; Markham, Dan A.; Eisenbrandt, David L.

doi:10.1093/toxsci/kfi196

Cited by 15 publications

(14 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…11-13) and in the ex vivo biodistribution data. Although the in vivo hydrolysis of fluorosulfate to sulfate and fluoride is known (23), it is unlikely to hamper the utility of the tracer in hNIS imaging because uptake at sites of NIS expression maximizes long before bone uptake is significant.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

et al. 2016

View full text Add to dashboard Cite

Anion transport by the human sodium-iodide symporter (hNIS) is an established target for molecular imaging and radionuclide therapy. Current radiotracers for PET of hNIS expression are limited to 124 I 2 and 18 F-BF 4 2 . We sought new 18 F-labeled hNIS substrates offering higher specific activity, higher affinity, and simpler radiochemical synthesis than 18 F-BF 4 2 . Methods: The ability of a range of anions, some containing fluorine, to block 99m TcO 4 2 uptake in hNIS-expressing cells was measured. SO 3 F 2 emerged as a promising candidate. 18 F-SO 3 F 2 was synthesized by reaction of 18 F 2 with SO 3 -pyridine complex in MeCN and purified using alumina and quaternary methyl ammonium solid-phase extraction cartridges. Chemical and radiochemical purity and serum stability were determined by radiochromatography. Radiotracer uptake and efflux in hNIS-transduced HCT116-C19 cells and the hNIS-negative parent cell line were evaluated in vitro in the presence and absence of a known competitive inhibitor (NaClO 4 ). PET/CT imaging and ex vivo biodistribution measurement were conducted on BALB/c mice, with and without NaClO 4 inhibition. Results: Fluorosulfate was identified as a potent inhibitor of 99m TcO 4 2 uptake via hNIS in vitro (half-maximal inhibitory concentration, 0.55-0.56 mM (in comparison with 0.29-4.5 mM for BF 4 2 , 0.07 mM for TcO 4 2 , and 2.7-4.7 mM for I 2 ). Radiolabeling to produce 18 F-SO 3 F 2 was simple and afforded high radiochemical purity suitable for biologic evaluation (radiochemical purity . 95%, decay-corrected radiochemical yield 5 31.6%, specific activity $ 48.5 GBq/mmol). Specific, blockable hNIS-mediated uptake in HCT116-C19 cells was observed in vitro, and PET/CT imaging of normal mice showed uptake in thyroid, salivary glands (percentage injected dose/g at 30 min, 563 6 140 and 32 6 9, respectively), and stomach (percentage injected dose/g at 90 min, 68 6 21). Conclusion: Fluorosulfate is a high-affinity hNIS substrate. 18 F-SO 3 F 2 is easily synthesized in high yield and very high specific activity and is a promising candidate for preclinical and clinical PET imaging of hNIS expression and thyroid-related disease; it is the first example of in vivo PET imaging with a tracer containing an S-18 F bond.

show abstract

Section: Discussionmentioning

confidence: 99%

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Comprehensive data on the physiological toxicity of SO 2 F 2 in various animal models can be found elsewhere. [105c] In insects [110] and rats, [111] fluoride ion derived from SO 2 F 2 hydrolysis is believed to be the primary toxin, although we think it likely that protein sulfation plays an important role. Fluorosulfation of proteins with SO 2 F 2 has been indicated in studies of food fumigation.…”

Section: Sulfuryl Fluoride Gas (So 2 F 2 ) As a Sulfur(vi) Connectormentioning

confidence: 99%

Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry

et al. 2014

View full text Add to dashboard Cite

Aryl sulfonyl chlorides (e.g. Ts-Cl) are beloved of organic chemists as the most commonly used S(VI) electrophiles, and the parent sulfuryl chloride, O2 S(VI) Cl2 , has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the S(VI) Cl bond is exceedingly sensitive to reductive collapse yielding S(IV) species and Cl(-) . Fortunately, the use of sulfur(VI) fluorides (e.g., R-SO2 -F and SO2 F2 ) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid-20th century. Here we seek to revive it, along with John Hyatt's unnoticed 1979 full paper exposition on CH2 CH-SO2 -F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2 F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of SF bonds for SO bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed.

show abstract

“…[108] Die Aufnahme von SO 2 F 2 in die Ozeane beträgt nur einen sehr geringen Prozentsatz der jährlichen Emissionen. [109] Entsprechend wurde spekuliert, dass alternative Mechanismen der SO [110] und Ratten [111] wird vermutet, dass das Fluoridion aus der SO 2 F 2 -Hydrolyse das primäre Toxin ist. Nach unserer Meinung ist es jedoch wahrscheinlich, dass Proteinsulfatierung eine wichtige Rolle spielt.…”

Section: Sulfurylfluoridgas (So 2 F 2 ) Als Schwefel(vi)-konnektorunclassified

Schwefel(VI)‐fluorid‐Austausch (SuFEx): Eine weitere gute Anwendung für die Click‐Chemie

et al. 2014

View full text Add to dashboard Cite

Arylsulfonylchloride (z. B. Ts‐Cl) sind die am häufigsten eingesetzten SVI‐Elektrophile in der organischen Synthesechemie, und auch die Stammverbindung, das Sulfurylchlorid (O2SVICl2), wurde zur Synthese von Sulfaten und Sulfamiden genutzt. Allerdings wird die gewünschte Halogenidsubstitution oftmals durch die Zersetzung des Schwefelelektrophils in SIV‐Spezies und Cl− verhindert, denn die SVI‐Cl‐Bindung ist äußerst reduktionsanfällig. Mit Schwefel(VI)‐fluoriden (z. B. R‐SO2‐F und SO2F2) verläuft die Umsetzung hingegen ausschließlich über den Substitutionsweg. Wie es bei der Click‐Chemie zumeist der Fall ist, wurden viele entscheidende Aspekte der Reaktivität von Schwefel(VI)‐fluoriden vor langer Zeit in Deutschland entdeckt.6a Überraschenderweise gerieten diese außerordentlichen Arbeiten in der Mitte des 20. Jahrhunderts ziemlich abrupt aus dem Blickfeld. In diesem Aufsatz versuchen wir, dieser Chemie neues Leben einzuhauchen. Insbesondere stützen wir uns dabei auch auf John Hyatts unbeachtet gebliebene Veröffentlichung über CH2CH‐SO2‐F aus dem Jahr 1979.98 Wir tragen mehrere neue Beobachtungen bei, einschließlich dem Befund, dass das ansonsten sehr stabile Gas SO2F2 eine exzellente Reaktivität unter den richtigen Umständen aufweist. Wir zeigen auch, dass Protonen oder Siliciumzentren den Austausch von S‐F‐Bindungen gegen S‐O‐Bindungen aktivieren können und dass der Sulfat‐Konnektor überraschend hydrolysestabil ist. Anwendungen dieser kontrollierbaren Ligationschemie auf kleine Moleküle, Polymere und Biomoleküle werden diskutiert.

show abstract

Rapid Uptake, Metabolism, and Elimination of Inhaled Sulfuryl Fluoride Fumigant by Rats

Cited by 15 publications

References 8 publications

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry

Schwefel(VI)‐fluorid‐Austausch (SuFEx): Eine weitere gute Anwendung für die Click‐Chemie

Contact Info

Product

Resources

About

Rapid Uptake, Metabolism, and Elimination of Inhaled Sulfuryl Fluoride Fumigant by Rats

Cited by 15 publications

References 8 publications

18F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

18F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry

Schwefel(VI)‐fluorid‐Austausch (SuFEx): Eine weitere gute Anwendung für die Click‐Chemie

Contact Info

Product

Resources

About

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo

¹⁸F-Fluorosulfate for PET Imaging of the Sodium–Iodide Symporter: Synthesis and Biologic Evaluation In Vitro and In Vivo