18F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography
Abstract
:1. Introduction
2. Results and discussion
2.1. Chemistry
2.2. Radiochemistry
2.3. Measurement of Partition Coefficient
2.4. Stability of [18F]3, [18F]4 and [18F]5
2.5. Cellular Accumulation of [18F]3, [18F]4 and [18F]5
2.6. Biodistribution of [18F]3, [18F]4 and [18F]5 in S180 Bearing Mice
Organs | Time (min) | ||||
---|---|---|---|---|---|
5 | 15 | 30 | 60 | 120 | |
Heart | 6.97 ± 0.47 | 5.08 ± 1.50 | 4.78 ± 0.36 | 3.63 ± 0.65 | 2.50 ± 0.67 |
Liver | 10.3 ± 0.44 | 6.03 ± 0.48 | 4.72 ± 0.81 | 2.97 ± 0.41 | 1.82 ± 0.079 |
Spleen | 6.92 ± 0.95 | 4.02 ± 0.90 | 3.14 ± 0.096 | 3.09 ± 0.69 | 1.66 ± 0.080 |
Lung | 6.21 ± 1.12 | 4.96 ± 1.08 | 4.02 ± 0.48 | 3.38 ± 0.38 | 1.88 ± 0.32 |
Kidney | 9.36 ± 0.25 | 4.97 ± 0.66 | 4.26 ± 0.29 | 2.94 ± 0.43 | 2.08 ± 0.26 |
Brain | 2.38 ± 0.17 | 2.30 ± 0.62 | 2.27 ± 0.69 | 2.18 ± 0.29 | 1.47 ± 0.14 |
Muscle | 6.64 ± 0.91 | 4.02 ± 1.03 | 3.79 ± 0.31 | 3.59 ± 0.43 | 2.12 ± 0.69 |
Blood | 6.09 ± 0.25 | 4.46 ± 0.18 | 4.43 ± 0.30 | 3.78 ± 0.56 | 2.59 ± 0.14 |
Tumor | 3.02 ± 0.36 | 3.45 ± 0.46 | 5.03 ± 0.68 | 3.96 ± 1.10 | 2.94 ± 0.27 |
Tumor/Brain | 1.27 | 1.50 | 2.21 | 1.82 | 2.00 |
Tumor/Muscle | 0.45 | 0.86 | 1.33 | 1.10 | 1.39 |
Tumor/Blood | 0.49 | 0.77 | 1.14 | 1.05 | 1.14 |
Organs | Time (min) | ||||
---|---|---|---|---|---|
5 | 15 | 30 | 60 | 120 | |
Heart | 6.67 ± 0.92 | 4.20 ± 1.0 | 5.07 ± 0.96 | 4.09 ± 0.59 | 3.61 ± 1.1 |
Liver | 10.7 ± 0.65 | 6.05 ± 0.56 | 4.61 ± 1.0 | 3.07 ± 0.35 | 2.32 ± 0.18 |
Spleen | 6.97 ± 0.34 | 3.87 ± 0.13 | 4.33 ± 1.3 | 2.99 ± 0.66 | 2.34 ± 0.69 |
Lung | 6.33 ± 0.87 | 4.06 ± 0.41 | 4.07 ± 0.18 | 3.24 ± 0.73 | 2.58 ± 0.30 |
Kidney | 11.1 ± 1.4 | 5.86 ± 0.14 | 4.2 ± 0.52 | 3.03 ± 0.55 | 2.58 ± 0.48 |
Brain | 1.75 ± 0.18 | 2.33 ± 0.26 | 2.95 ± 0.56 | 2.26 ± 0.49 | 1.6 ± 0.16 |
Muscle | 6.48 ± 1.0 | 3.75 ± 0.32 | 4.19 ± 0.65 | 3.28 ± 0.71 | 1.54 ± 0.39 |
Blood | 6.33 ± 0.45 | 4.91 ± 0.46 | 4.57 ± 0.59 | 3.64 ± 0.40 | 3.30 ± 0.22 |
Tumor | 1.91 ± 1.2 | 3.84 ± 0.46 | 4.41 ± 1.3 | 4.53 ± 0.90 | 3.75 ± 0.21 |
Tumor/Brain | 1.09 | 1.65 | 1.5 | 2.01 | 2.35 |
Tumor/Muscle | 0.29 | 1.03 | 1.05 | 1.38 | 2.44 |
Tumor/Blood | 0.30 | 0.78 | 0.96 | 1.25 | 1.14 |
Organs | Time (min) | ||||
---|---|---|---|---|---|
5 | 15 | 30 | 60 | 120 | |
Heart | 3.02 ± 0.51 | 1.19 ± 0.21 | 0.97 ± 0.19 | 0.42 ± 0.07 | 0.52 ± 0.05 |
Liver | 10.39 ± 1.86 | 2.90 ± 0.86 | 2.29 ± 0.38 | 1.79 ± 0.38 | 1.63 ± 0.22 |
Spleen | 3.10 ± 0.12 | 2.76 ± 0.11 | 0.54 ± 0.07 | 0.55 ± 0.19 | 0.53 ± 0.02 |
Lung | 16.34 ± 1.80 | 15.13 ±1.57 | 6.35 ± 1.28 | 2.45 ± 0.55 | 4.09 ± 0.19 |
Kidney | 12.70 ± 0.90 | 3.71 ± 0.69 | 2.21 ± 0.29 | 0.94 ± 0.28 | 0.58 ± 0.01 |
Brain | 0.22 ± 0.00 | 0.14 ± 0.00 | 0.15 ± 0.02 | 0.15 ± 0.00 | 0.14 ± 0.00 |
Muscle | 2.15 ± 0.66 | 1.07 ± 0.35 | 0.49 ± 0.09 | 0.54 ± 0.00 | 0.18 ± 0.04 |
Blood | 6.68 ± 0.05 | 2.24 ± 0.04 | 0.95 ± 0.10 | 0.45 ± 0.09 | 0.35 ± 0.02 |
Tumor | 2.55 ± 0.42 | 1.75 ± 0.54 | 1.30 ± 0.15 | 0.71 ± 0.11 | 0.83 ± 0.17 |
Tumor/Brain | 11.59 | 12.5 | 8.67 | 4.73 | 5.93 |
Tumor/Muscle | 1.19 | 1.64 | 2.65 | 1.31 | 4.61 |
Tumor/Blood | 0.38 | 0.78 | 1.37 | 1.58 | 2.37 |
2.7. MicroPET Imagings of [18F]3 in S180 Bearing Mouse
3. Experimental
3.1. General
3.2. Synthesis
3.3. Octanol/Water Partition Coefficient
3.4. Quality Control of Purified Radiotracers
3.5. Stability Study
3.6. Cellular Accumulation Studies
3.7. Biodistribution and MicroPET Imaging Studies in S180 Tumor Bearing Mice
3.8. Statistical Analysis
4. Conclusions
Supplementary Materials
Acknowledgments
References and Notes
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Xu, J.; Liu, H.; Li, G.; He, Y.; Ding, R.; Wang, X.; Feng, M.; Zhang, S.; Chen, Y.; Li, S.; et al. 18F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography. Molecules 2012, 17, 3774-3793. https://doi.org/10.3390/molecules17043774
Xu J, Liu H, Li G, He Y, Ding R, Wang X, Feng M, Zhang S, Chen Y, Li S, et al. 18F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography. Molecules. 2012; 17(4):3774-3793. https://doi.org/10.3390/molecules17043774
Chicago/Turabian StyleXu, Jingli, Hang Liu, Guixia Li, Yong He, Rui Ding, Xiao Wang, Man Feng, Shuting Zhang, Yurong Chen, Shilei Li, and et al. 2012. "18F-labeled Pyrazolo[1,5-a]pyrimidine Derivatives: Synthesis from 2,4-Dinitrobenzamide and Tosylate Precursors and Comparative Biological Evaluation for Tumor Imaging with Positron Emission Tomography" Molecules 17, no. 4: 3774-3793. https://doi.org/10.3390/molecules17043774