CycloSiFA: Die nächste Generation von Silicium‐basierten Fluoridakzeptoren für die Positronenemissionstomographie (PET) DOI Creative Commons
Matthias Mawick,

Carolin Jaworski,

Jens Bittermann

et al.

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(50)

Published: Oct. 18, 2023

Abstract Die ringöffnende Si‐Fluorierung einer Vielzahl von Azasilolderivaten Cyclo ‐1‐( i Pr 2 Si)−4‐X−C 6 H 3 −2‐CH NR ( 4 : R=2,6‐ C , X=H; a R=2,4,6‐Me 9 X= t BuMe SiO; 10 X=OH; 13 X=HCCCH O; 22 SiCH O) mit verschiedenen 19 F‐Fluoridquellen untersucht, optimiert und die gewonnenen Erfahrungen in einem translationalen Ansatz genutzt, um ein einfaches 18 F‐Markierungsprotokoll für Azasilolderivate [ F] 14 zu erstellen. Letzteres stellt eine potenziell klickbare SiFA‐prothetische Gruppe dar, bei der Entwicklung PET‐Tracern unter Verwendung Cu‐katalysierten Triazolbildung eingesetzt werden könnte. Auf Grundlage unserer Ergebnisse hat SiFA das Potenzial, neuer Einstieg nicht‐kanonische Markierungsmethoden radioaktiver PET‐Tracer werden.

Click Chemistry and Radiochemistry: An Update DOI Creative Commons
David Bauer, Mike Cornejo,

Tran Hoang

et al.

Bioconjugate Chemistry, Journal Year: 2023, Volume and Issue: 34(11), P. 1925 - 1950

Published: Sept. 22, 2023

The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists combine molecular subunits as if they puzzle pieces. Over the last 25 years, click chemistry toolbox has swelled from canonical copper-catalyzed azide–alkyne cycloaddition encompass an array ligations, including bioorthogonal variants, such strain-promoted inverse electron-demand Diels–Alder reaction. Without question, rise impacted all areas biological science. Yet unique traits radiopharmaceutical have made it particularly fertile ground for this technology. In update, we seek provide comprehensive guide recent developments at intersection illuminate several exciting trends field, use emergent radiosynthesis, clinical translation novel probes synthesized using chemistry, advent click-based vivo pretargeting.

Language: Английский

Citations

35
Preclinical and First-In-Human Imaging of Novel [18F]F-FAPI-FUSCC-07 Tracer: Comparative Prospective Study with [18F]F-FAPI-42 and [18F]F-FAPI-74 DOI
Linjie Bian, Xinyu Liu, Xiao Wang

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

This study aimed to develop and evaluate a novel fibroblast activation protein (FAP)-specific tracer, fluorine-18-labeled inhibitor-FUSCC-07 ([18F]F-FAPI-FUSCC-07), for use in both preclinical clinical settings. Preclinical evaluations were conducted assess the stability partition coefficient of [18F]F-FAPI-FUSCC-07. Experiments involving human glioma U87MG cells demonstrated its cellular uptake inhibitory properties. Further investigations included biodistribution analysis micropositron emission tomography/computed tomography (PET/CT) imaging tumor-bearing mice, which revealed strong tumor prolonged retention. In setting, [18F]F-FAPI-FUSCC-07 was compared directly with [18F]F-FAPI-42 [18F]F-FAPI-74 performance various cancers. By expanding patient cohort, provided more comprehensive assessment tracer lesions. The findings that exhibited high phosphate-buffered saline fetal bovine serum, as well hydrophilic Clinical results indicated significantly higher improved target-to-blood pool ratios other tracers. Moreover, PET patients diverse cancers showed consistently superior image contrast most cases. These represent first evidence supporting feasibility across multiple types. highlights potential promising FAPI imaging, offering enhanced diagnostic precision broader applicability oncology.

Language: Английский

Citations

1
Desmethyl SuFEx-IT: SO2F2-Free Synthesis and Evaluation as a Fluorosulfurylating Agent DOI Creative Commons
Jan Bertram, Felix Neumaier, Boris D. Zlatopolskiy

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(6), P. 3821 - 3833

Published: Feb. 22, 2024

Access to SuFExable compounds was remarkably simplified by introduction of the solid FO2S-donor SuFEx-IT. However, published process for preparation this reagent relies on use sulfuryl fluoride (SO2F2), which is difficult obtain and highly toxic. Herein, we disclose a simple protocol SO2F2-free, hectogram-scale analogous desmethyl SuFEx-IT from inexpensive starting materials. The prepared in high (85%) total yield without chromatographic purification steps. In addition, demonstrate utility successful series fluorosulfates sulfamoyl fluorides excellent yields. As such, our work recognizes as valuable alternative common FO2S-donors enables cost-efficient access substrates SuFEx click chemistry.

Language: Английский

Citations

8
Click chemistry-aided drug discovery: A retrospective and prospective outlook DOI
Rui Zhao, Junlong Zhu, Xiaoying Jiang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 264, P. 116037 - 116037

Published: Dec. 12, 2023

Language: Английский

Citations

14
Study of Carbamoyl Fluoride: Synthesis, Properties and Applications DOI
Clémence Bonnefoy, Emmanuel Chefdeville,

Christian Tourvieille

et al.

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(43)

Published: May 31, 2022

Abstract Carbamoyl fluoride is a fluorinated group that, to this date, remains underexplored, probably due the lack of data concerning its properties. In paper, study carbamoyl presented. Stability studies, in particular under physiological conditions, and lipophilicity measurement were performed. A new easy, safe, inexpensive, metal‐free synthesis method also described. Finally, potential use radiochemistry through 18 F/ 19 F isotopic exchange demonstrated.

Language: Английский

Citations

19
Advances in sulfur fluoride exchange for chemical biology DOI
Tobias Hansen,

Marcos San Segundo,

Annika M. Mergel

et al.

Trends in Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Direct 18F-Fluorosulfurylation of Phenols and Amines Using an [18F]FSO2+ Transfer Agent Generated In Situ DOI

Min Pyeong Kim,

Hojin Cho,

Swatilekha Kayal

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(9), P. 6263 - 6273

Published: April 10, 2023

We report the direct radiofluorosulfurylation method for synthesis of 18F-labeled fluorosulfuryl derivatives from phenols and amines using an [18F]FSO2+ transfer agent generated in situ. Nucleophilic radiofluorination is achieved even a hydrous organic medium, obviating need azeotropic drying use cryptands. This unprecedented, operationally simple isotopic functionalization facilitates reliable production potential radiotracers positron emission tomography, rendering facile access to SuFEx radiochemistry.

Language: Английский

Citations

9
Preparation of 18F-Labeled Tracers Targeting Fibroblast Activation Protein via Sulfur [18F]Fluoride Exchange Reaction DOI Creative Commons
Austin Craig, Jürgen Kogler, Markus Laube

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(12), P. 2749 - 2749

Published: Dec. 10, 2023

Early detection and treatment of cancers can significantly increase patient prognosis enhance the quality life affected patients. The emerging significance tumor microenvironment (TME) as a new frontier for cancer diagnosis therapy may be exploited by radiolabeled tracers diagnostic imaging techniques such positron emission tomography (PET). Cancer-associated fibroblasts (CAFs) within TME are identified biomarkers fibroblast activation protein alpha (FAPα), which expressed on their surfaces. Targeting FAPα using small-molecule 18F-labeled inhibitors (FAPIs) has recently garnered significant attention non-invasive visualization PET. Herein, two potent aryl-fluorosulfate-based FAPIs, 12 13, were synthetically prepared, inhibition potency was determined fluorimetric FAP assay to IC50 9.63 4.17 nM, respectively. Radiofluorination performed via sulfur [18F]fluoride exchange ([18F]SuFEx) reaction furnish [18F]12 [18F]13 in high activity yields (AY) 39-56% molar activities (Am) between 20-55 GBq/µmol. In vitro experiments focused stability FAPIs after incubation with human serum, liver microsomes cytosol. Preliminary PET studies radioligands healthy mice investigate vivo biodistribution 18F defluorination rate. Fast pharmacokinetics FAP-targeting retained considerable bone uptake, caused either or radioligand accumulation, observed. summary, our findings demonstrate efficiency [18F]SuFEx radiolabeling method well its advantages limitations respect tracer development.

Language: Английский

Citations

7
Design, synthesis and evaluation of novel prostate-specific membrane antigen-targeted aryl [18F]fluorosulfate PET tracers DOI
Zhaolin Wang, Bin Zhu, Fan Jiang

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 106, P. 117753 - 117753

Published: May 1, 2024

Language: Английский

Citations

2
An Investigation into the In Vitro Metabolic Stability of Aryl Sulfonyl Fluorides for their Application in Medicinal Chemistry and Radiochemistry DOI
Andrew T. King, Lidia Matesic, Sinead T. Keaveney

et al.

Molecular Pharmaceutics, Journal Year: 2023, Volume and Issue: 20(2), P. 1061 - 1071

Published: Jan. 13, 2023

Molecules that feature a sulfonyl fluoride (SO2F) moiety have been gaining increasing interest due to their unique reactivity and potential applications in synthetic chemistry, medicinal other biological uses. A particular is towards 18F-radiochemistry where fluorides can be used as method radiolabel biomolecules or radiofluoride relay reagents facilitate radiolabeling of molecules. The low metabolic stability S–F bonds, however, presents an issue limits the applicability fluorides. aim this work was increase understanding what features contribute instability bond model aryl identify approaches for medicinal, chemistry applications. To undertake this, 14 compounds with varying functional groups substitution patterns were investigated, stabilities examined various media, including phosphate-buffered saline rat serum conditions. results indicate both electronic steric factors affect bond, 2,4,6-trisubstituted displaying highest vitro stability.

Language: Английский

Citations

5