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@INPROCEEDINGS{Hoffmann:1026459,
author = {Hoffmann, Chris and Bertram, Jan and Endepols, Heike and
Zlatopolskiy, Boris and Neumaier, Bernd},
title = {{P}reparation of radiolabeled sulfamoyl fluorides by
{S}u{FE}x 18{F}/19{F} isotopic exchange and assessment of
their in vivo stability},
reportid = {FZJ-2024-03408},
year = {2023},
abstract = {Objectives: Aryl fluorosulfates (FO 2 S-O-) and
disubstituted sulfa-moyl fluorides (FO 2S-N-) often possess
high hydrolytic stability and arewidely used in chemical
biology and drug design. Recently we reporteda protocol for
convenient preparation of radiolabeled aryl fluorosul-fates
with high molar activity via fast 18 F/19 F isotopic
exchange [1]. Theaim of the present work was to study the
suitability of this procedurefor radiofluorination of
sulfamoyl fluorides. To this end, the procedurewas applied
to N-sulfamoylated indole and carbazole as well as tothree
protected amino acids (Boc-Trp(SO2 F)-OMe 1,
Boc-His(SO2F)-OMe 2 and Boc-2,3-DH-Trp(SO2 F)-OMe 3).
Additionally, the in vivostability of the radiolabeled
tryptophan derivative Boc-Trp([18 F]SO2F)-OMe ([18 F]1) was
evaluated.Methods: Aqueous [18 F]fluoride was loaded onto an
anionexchange QMA cartridge and eluted with Et 4NOH (10
μmol) inMeOH (1 mL). MeOH was evaporated, a solution of the
correspondingsubstrate (31–125 nmol) in MeCN (500 μL) was
added and the reactionmixture was stirred for 7 min at 40
°C. Thereafter, H2 O (1 mL) wasadded and radiochemical
conversions (RCCs) were determined byradio-HPLC. [ 18 F]1
was isolated by solid phase extraction using aStrataX C18
cartridge. The tracer was formulated in Tween® 20 (200
μL)and 1 mm sodium phosphate buffer (2 μL; pH 7.2) and
subjected to apreclinical evaluation in healthy mice using
μPET.Results: Radiolabeled N–sulfamoyl fluorides of
carbazole andindole were prepared in RCCs of 72 ± $2\%$ and
86 ± $2\%,$ respectively.FO 2SN-functionalized protected
tryptophan 1 (RCC: 68 ± $5\%),$ histidine2 (RCC: 3 ±
$1\%)$ and 2,3-dihydroxy-tryptophan 3 (RCC: $34\%;$ 60°C,14
min), were also successfully radiofluorinated. Boc-Trp([18
F]SO2F)-OMe [18 F]1 was isolated in activity yields of 24 ±
$2\%$ with aradiochemical purity of $99\%$ (n = 3) within 70
min using 12.5 μg (31 nmol) of precursor. In μPET
experiments, the radiolabeled productshowed very low
radioactivity accumulation in bones, indicating a lackof
significant in vivo defluorination. The study also
demonstratedalmost exclusive hepatobiliary elimination of
the tracer, presumablyowing to its very high
lipophilicity.Conclusions: The SuFEx protocol developed for
radiolabeling offluorosulfates was successfully applied for
the simple and fastpreparation of 18 F-labeled sulfamoyl
fluorides. High metabolic stabilityof Boc-Trp(SO2 [
18F]F)-OMe underlines the suitability of this class
ofradiolabeled compounds as PET-probes for in vivo
imaging.Reference[1] Walter N., Bertram J., Drewes B.,
Bahutski V., Timmer M., SchützM. B., Krämer F., Neumaier
F., Endepols H., Neumaier B.,Zlatopolskiy B. D., European
Journal of Medicinal Chemistry2022, 237, 114383.},
month = {May},
date = {2023-05-22},
organization = {25th International Symposium on
Radiopharmaceutical Sciences, Honolulu,
USA (USA), 22 May 2023 - 26 May 2023},
subtyp = {After Call},
cin = {INM-5},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)6},
url = {https://juser.fz-juelich.de/record/1026459},
}