Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Structure–Activity Relationship (SAR) Studies
2.3. Radiochemistry
2.4. Metabolite Analysis
2.5. Autoradiography Study
2.6. PET Studies
3. Materials and Methods
3.1. General Information
3.2. Chemical Synthesis
3.2.1. Synthesis of 4-(furan-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine (3)
3.2.2. General Procedure A
3.2.3. General Procedure B
3.2.4. General Procedure C
3.3. Docking Stimulation
3.4. Radiosynthesis
3.4.1. Preparation [18F]TBAF Complex
3.4.2. Radiosynthesis of [18F]PPY1
3.4.3. Radiosynthesis of [18F]PPY2
3.5. Quality Control
3.6. In Vitro Stability and Lipophilicity (LogD7.4)
3.7. Biological Evaluation
3.8. In Vitro Binding Assays
3.9. In Vitro Autoradiography
3.10. In Vivo Metabolism
3.11. PET Imaging
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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R | Ki(hA2AR) in nM | Ki(hA1R) in nM | R | Ki(hA2AR) in nM | Ki(hA1R) in nM | ||
PPY1 | 5.29 ± 1.35 | 220 (235, 205) | PPY12 | 66.7 (83.4, 50.0) | 810 (821, 799) | ||
PPY2 | 2.13 ± 0.42 (Lit.: 4) [39] | 147 (165, 129) (Lit.: 264) [39] | PPY13 | 310 (369, 250) | 1452 (2298, 606) | ||
PPY3 | 3.60 ± 1.29 | 132 (125, 140) | PPY14 | 291 (297, 285) | 954 (682, 1226) | ||
PPY4 | 47.8 ± 4.8 | 822 (839, 805) | PPY15 | 12.3 (15.6, 8.98) | 470 (637, 302) | ||
PPY5 | 25.7 ± 0.9 | 689 (709, 669) | PPY16 | 1.63 ± 0.22 | 69.2 ± 32.8 | ||
PPY6 | 27.1 ± 2.6 | 566 (574, 558) | PPY17 | 4.50 ± 0.99 | 215 ± 38 | ||
PPY7 | 161 ± 19 | 2879 (3036, 2722) | PPY18 | 76.8 ± 12.9 | 527 ± 574 | ||
PPY8 | 0.93 ± 0.10 | 31.3 ± 15.5 | PPY19 | 107 (114, 99.9) | 245 (259, 231) | ||
PPY9 | 34.1 (40.5, 27.6) | 766 (743, 489) | PPY20 | 275 (287, 263) | 1417 (1529, 1304) | ||
PPY10 | 14.2 (15.1, 13.2) | 160 (217, 103) | PPY21 | 283 (293, 273) | 1551 (1816, 1285) | ||
PPY11 | 2.35 ± 0.30 | 162 ± 22 | PPY22 | 1.68 ± 0.14 (Lit.: 3) [39] | 155 ± 15 (Lit.: 68) [39] |
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Lai, T.H.; Schröder, S.; Toussaint, M.; Dukić-Stefanović, S.; Kranz, M.; Ludwig, F.-A.; Fischer, S.; Steinbach, J.; Deuther-Conrad, W.; Brust, P.; et al. Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation. Int. J. Mol. Sci. 2021, 22, 2285. https://doi.org/10.3390/ijms22052285
Lai TH, Schröder S, Toussaint M, Dukić-Stefanović S, Kranz M, Ludwig F-A, Fischer S, Steinbach J, Deuther-Conrad W, Brust P, et al. Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation. International Journal of Molecular Sciences. 2021; 22(5):2285. https://doi.org/10.3390/ijms22052285
Chicago/Turabian StyleLai, Thu Hang, Susann Schröder, Magali Toussaint, Sladjana Dukić-Stefanović, Mathias Kranz, Friedrich-Alexander Ludwig, Steffen Fischer, Jörg Steinbach, Winnie Deuther-Conrad, Peter Brust, and et al. 2021. "Development of 18F-Labeled Radiotracers for PET Imaging of the Adenosine A2A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation" International Journal of Molecular Sciences 22, no. 5: 2285. https://doi.org/10.3390/ijms22052285