Synthesis, Fluorine-18 Radiolabeling, and In Vivo PET Imaging of a Hydrophilic Fluorosulfotetrazine
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of the Fluorosulfotetrazine 1
2.2. IEDDA Reaction of the Fluorosulfotetrazine 1 with TCO Reagent 9
2.3. Development of the Radiosynthesis of [18F]Fluorosulfotetrazine [18F]1
2.4. Automated Radiosynthesis of [18F]Fluorosulfotetrazine [18F]1
2.5. Quality Control
2.6. LogP and LogD7.4 Measurements
2.7. In Vitro Stability Studies
2.8. In Vivo Biodistribution Using PET/MR in Mice
2.9. Radiometabolite Analysis of Mouse Plasma Samples
3. Materials and Methods
3.1. Chemical Syntheses
3.1.1. General
3.1.2. 3-(Prop-2-yn-1-yl)-1,2-oxathiane 2,2-dioxide 3
3.1.3. 7-(Fluoro)hept-1-yne-4-sulfonic Acid 4
3.1.4. 4-(Azidomethyl)benzonitrile 6
3.1.5. 3-(4-(Azidomethyl)phenyl)-6-methyl-1,2,4,5-tetrazine 7
3.1.6. 3-((1-(4-(6-Methyl-1,2,4,5-tetrazin-3-yl)benzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2-oxathiane 2,2-dioxide 8
3.1.7. 5-(Fluoro)-1-(1-(4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzyl)-1H-1,2,3-triazol-4-yl)pentane-2-sulfonic Acid 1
3.2. Automated Radiosynthesis of [18F]1
3.2.1. General
3.2.2. 5-([18F]Fluoro)-1-(1-(4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzyl)-1H-1,2,3-triazol-4-yl)pentane-2-sulfonic Acid [18F]1
3.3. Radiochemical and Chemical Purities, and Molar Activity of [18F]1
3.4. LogP and LogD7.4 Calculations
3.5. In Vitro Stability Studies
3.6. Animal Studies
3.6.1. General Considerations
3.6.2. PET Imaging Experiments
3.6.3. In Vivo Stability Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Beaufrez, J.; Guillouet, S.; Seimbille, Y.; Perrio, C. Synthesis, Fluorine-18 Radiolabeling, and In Vivo PET Imaging of a Hydrophilic Fluorosulfotetrazine. Pharmaceuticals 2023, 16, 636. https://doi.org/10.3390/ph16050636
Beaufrez J, Guillouet S, Seimbille Y, Perrio C. Synthesis, Fluorine-18 Radiolabeling, and In Vivo PET Imaging of a Hydrophilic Fluorosulfotetrazine. Pharmaceuticals. 2023; 16(5):636. https://doi.org/10.3390/ph16050636
Chicago/Turabian StyleBeaufrez, Jason, Stéphane Guillouet, Yann Seimbille, and Cécile Perrio. 2023. "Synthesis, Fluorine-18 Radiolabeling, and In Vivo PET Imaging of a Hydrophilic Fluorosulfotetrazine" Pharmaceuticals 16, no. 5: 636. https://doi.org/10.3390/ph16050636
APA StyleBeaufrez, J., Guillouet, S., Seimbille, Y., & Perrio, C. (2023). Synthesis, Fluorine-18 Radiolabeling, and In Vivo PET Imaging of a Hydrophilic Fluorosulfotetrazine. Pharmaceuticals, 16(5), 636. https://doi.org/10.3390/ph16050636