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| Home > Publications database > Preparation of radiolabeled sulfamoyl fluorides by SuFEx 18F/19F isotopic exchange and assessment of their in vivo stability |
| Conference Presentation (After Call) | FZJ-2024-03408 |
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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.
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