Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma
Abstract
:1. Introduction
2. Results
2.1. The Preparation of 18F-FPABZA and 18F-FNABZA
2.2. Partition Coefficient Determination and In Vitro Stability of 18F-FPABZA or 18F-FNABZA
2.3. In Vitro Binding of 18F-FPABZA and 18F-FNABZA to Melanin
2.4. In Vitro Cellular Uptake Study of 18F-FPABZA and 18F-FNABZA in Melanoma Cells
2.5. MicroPET Imaging
2.6. Biodistribution Study
3. Discussion
4. Materials and Methods
4.1. Reagents and Instruments
4.2. Preparation of 18F-FPABZA and 18F-FNABZA
4.2.1. Synthesis of 4-Amino-N-(2-(diethylamine)ethyl)-2-methoxybenzamide (1)
4.2.2. Synthesis of N-(4-((2-Diethylamino)ethyl)carbamoyl-5-methoxyphenyl)-picolinamide (2a) and Synthesis of N-(4-((2-diethylamino)ethyl)carbamoyl-5-methoxyphenyl)-nicotinamide (2b)
4.2.3. Radiolabeling of 18F-FPABZA (3a) and 18F-FNABZA (3b)
4.2.4. Synthesis of N-(4-((2-(Diethylamino)ethyl)carbamoyl)-3-methoxyphenyl)-5-fluoropicolinamide (4a) and N-(4-((2-(diethylamino)ethyl)carbamoyl)-3-methoxyphenyl)-6-fluoronicotinamide (4b)
4.3. Partition Coefficient Determination of 18F-FPABZA or 18F-FNABZA
4.4. In Vitro Stability of 18F-FPABZA
4.5. Binding Affinity to Melanin Assays
4.6. Cellular Uptake Studies
4.7. Establishment of Melanoma-Bearing Mouse Models
4.8. MicroPET Scanning
4.9. MicroPET Scanning
5. 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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Organ | 15 min | 30 min | 60 min | 120 min |
---|---|---|---|---|
Blood | 3.70 ± 0.80 | 2.67 ± 0.83 | 0.95 ± 0.24 | 0.24 ± 0.17 |
Heart | 4.74 ± 0.80 | 2.69 ± 0.75 | 1.00 ± 0.26 | 0.68 ± 0.69 |
Lung | 8.22 ± 1.87 | 4.58 ± 1.82 | 1.82 ± 0.56 | 1.24 ± 1.34 |
Liver | 5.32 ± 2.04 | 3.69 ± 1.01 | 1.63 ± 0.37 | 1.32 ± 1.00 |
Stomach | 4.95 ± 1.99 | 3.69 ± 1.35 | 1.78 ± 0.85 | 0.78 ± 0.39 |
Small int. | 5.60 ± 0.98 | 7.35 ± 1.45 | 5.01 ± 2.64 | 1.39 ± 0.52 |
Large int. | 4.64 ± 0.65 | 2.71 ± 0.28 | 1.91 ± 1.00 | 1.20 ± 0.32 |
Spleen | 11.73 ± 1.37 | 5.75 ± 1.85 | 3.16 ± 1.08 | 0.54 ± 0.07 |
Pancreas | 12.80 ± 5.60 | 4.99 ± 1.96 | 1.93 ± 0.67 | 0.80 ± 0.22 |
Bone | 1.84 ± 0.39 | 1.85 ± 0.48 | 1.40 ± 0.51 | 1.40 ± 0.17 |
Muscle | 3.32 ± 1.45 | 2.34 ± 0.81 | 0.71 ± 0.19 | 0.44 ± 0.65 |
Tumor | 12.32 ± 4.13 | 13.21 ± 3.91 | 20.57 ± 2.22 | 16.89 ± 2.32 |
Brain | 3.30 ± 0.12 | 1.26 ± 0.28 | 0.39 ± 0.12 | 0.10 ± 0.04 |
Kidneys | 15.57 ± 1.71 | 10.82 ± 4.29 | 3.78 ± 1.19 | 2.39 ± 2.22 |
Eye ball | 20.40 ± 4.81 | 25.74 ± 3.23 | 36.91 ± 3.49 | 33.61 ± 2.14 |
Urine | 103.75 ± 87.59 | 282.89 ± 115.42 | 276.62 ± 152.36 | 90.79 ± 68.19 |
Fece | 6.92 ± 3.79 | 7.37 ± 1.47 | 12.18 ± 8.56 | 12.13 ± 2.86 |
Ratios | ||||
Tumor/muscle | 6.97 ± 1.96 | 6.66 ± 3.16 | 26.47 ± 3.11 | 86.57 ± 5.39 |
Tumor/blood | 4.40 ± 1.22 | 5.18 ± 1.66 | 19.89 ± 1.19 | 51.93 ± 18.05 |
Tumor/liver | 2.46 ± 0.38 | 3.73 ± 1.10 | 11.03 ± 2.40 | 23.61 ± 9.04 |
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Lo, Y.-H.; Chang, T.-Y.; Chen, C.-L.; Lin, M.-H.; Wang, H.-E.; Chang, C.-W.; Liu, R.-S.; Wu, C.-Y. Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma. Int. J. Mol. Sci. 2021, 22, 6432. https://doi.org/10.3390/ijms22126432
Lo Y-H, Chang T-Y, Chen C-L, Lin M-H, Wang H-E, Chang C-W, Liu R-S, Wu C-Y. Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma. International Journal of Molecular Sciences. 2021; 22(12):6432. https://doi.org/10.3390/ijms22126432
Chicago/Turabian StyleLo, Yi-Hsuan, Ting-Yu Chang, Chuan-Lin Chen, Ming-Hsien Lin, Hsin-Ell Wang, Chi-Wei Chang, Ren-Shyan Liu, and Chun-Yi Wu. 2021. "Development of Radiofluorinated Nicotinamide/Picolinamide Derivatives as Diagnostic Probes for the Detection of Melanoma" International Journal of Molecular Sciences 22, no. 12: 6432. https://doi.org/10.3390/ijms22126432