Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain
Abstract
:1. Introduction
2. Results and Discussion
2.1. Organic Chemistry
2.2. In Vitro Binding Assay
2.3. Radiochemistry
2.4. In Vitro Evaluation of [18F]LU14
2.5. In Vivo Metabolism
2.6. PET Imaging
3. Materials and Methods
3.1. Chemistry
3.1.1. General Information
3.1.2. Chemical Synthesis
3.2. Radiochemistry
3.2.1. Automated Radiosynthesis of [18F]LU14
3.2.2. Quality Control
3.2.3. Determination of Lipophilicity (LogD7.4)
3.3. Biological Experiments
3.3.1. Determination of Binding Affinities by Homogenate Assays
3.3.2. In Vitro Autoradiography
3.3.3. Quantification of Radiometabolites
3.3.4. PET 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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TAC Parameter | hCB2R(D80N) | Contralateral | p-Value | Cerebellum | p-Value |
---|---|---|---|---|---|
time to peak (min) | 7.4 ± 2.8 | 3.8 ± 1.6 | 0.063 | 1.6 ± 1.4 | 0.016 |
TAC peak value (SUV) | 3.3 ± 0.6 | 2.2 ± 0.4 | 0.024 | 2.7 ± 0.0 | 0.067 |
AUC (SUV × min) | 155 ± 28 | 42.6 ± 6.8 | 0.001 | 41.1 ± 5.6 | 0.001 |
AUMC (SUV × min2) | 4349 ± 701 | 854 ± 165 | 0.001 | 819 ± 132 | 0.001 |
MRT (min) | 28.0 ± 0.4 | 20.0 ± 1.1 | <0.001 | 19.9 ± 1.2 | <0.001 |
hCB2R D80N-to- | Treatment (5 mg/kg GW405833, i.v.) | AUC0–20min (CI95%) in SUVr × min | AUC40–60min (CI95%) in SUVr × min |
---|---|---|---|
contralateral | vehicle (10 min pior tracer) | 40 (37 to 42) | 210 (190 to 231) |
displacement (20 min after tracer) | 48 (41 to 54) | 56 (50 to 62) −73.4% | |
cerebellum | vehicle (10 min prior tracer) | 44 (39 to 48) | 215 (190 to 241) |
displacement (20 min after tracer) | 49 (40 to 59) | 51 (42 to 60) −76.3% |
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Teodoro, R.; Gündel, D.; Deuther-Conrad, W.; Ueberham, L.; Toussaint, M.; Bormans, G.; Brust, P.; Moldovan, R.-P. Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain. Int. J. Mol. Sci. 2021, 22, 8051. https://doi.org/10.3390/ijms22158051
Teodoro R, Gündel D, Deuther-Conrad W, Ueberham L, Toussaint M, Bormans G, Brust P, Moldovan R-P. Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain. International Journal of Molecular Sciences. 2021; 22(15):8051. https://doi.org/10.3390/ijms22158051
Chicago/Turabian StyleTeodoro, Rodrigo, Daniel Gündel, Winnie Deuther-Conrad, Lea Ueberham, Magali Toussaint, Guy Bormans, Peter Brust, and Rareş-Petru Moldovan. 2021. "Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain" International Journal of Molecular Sciences 22, no. 15: 8051. https://doi.org/10.3390/ijms22158051