Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Radiochemistry
2.2.1. Synthesis of 99mTcN-MAG-ADMQ and 99mTcN-MAG3-ADMQ
2.2.2. In Vitro Stability
2.2.3. Paper Electrophoresis
2.2.4. Partition coefficients
[99mTcN]-1 | [99mTcN]-2 | |
---|---|---|
log P | −1.81 ± 0.02 | −1.57 ± 0.01 |
2.2.5. Biological Evaluation
Tissue | 30 min | 60 min | 120 min |
---|---|---|---|
Heart | 0.27 ± 0.02 | 0.11 ± 0.01 | 0.05 ± 0.01 |
Liver | 2.71 ± 0.16 | 1.01 ± 0.08 | 0.55 ± 0.11 |
Spleen | 0.31 ± 0.03 | 0.15 ± 0.01 | 0.07 ± 0.02 |
Lung | 1.36 ± 0.13 | 0.94 ± 0.06 | 0.44 ± 0.09 |
Kidney | 2.42 ± 0.10 | 2.3 ± 0.07 | 1.35 ± 0.11 |
Muscle | 0.27 ± 0.01 | 0.07 ± 0.01 | 0.06 ± 0.02 |
Bone | 0.19 ± 0.02 | 0.16 ± 0.04 | 0.04 ± 0.01 |
Large Intestine | 0.71 ± 0.22 | 0.79 ± 0.12 | 0.51 ± 0.10 |
Small Intestine | 0.31 ± 0.01 | 0.25 ± 0.03 | 0.18 ± 0.03 |
Stomach | 0.43 ± 0.05 | 0.04 ± 0.01 | 0.07 ± 0.03 |
Brain | 0.04 ± 0.01 | 0.03 ± 0.02 | 0.01 ± 0.01 |
Tumor | 0.35 ± 0.03 | 0.31 ± 0.04 | 0.07 ± 0.01 |
Blood | 1.09 ± 0.11 | 0.82 ± 0.03 | 0.11 ± 0.04 |
T/M ratio | 1.29 ± 0.14 | 1.82 ± 0.33 | 1.17 ± 0.13 |
T/B ratio | 1.84 ± 0.07 | 1.94 ± 0.24 | 1.75 ± 0.16 |
Tissue | 30 min | 60 min | 120 min |
---|---|---|---|
Heart | 0.40 ± 0.05 | 0.12 ± 0.03 | 0.08 ± 0.01 |
Liver | 0.78 ± 0.09 | 0.79 ± 0.04 | 0.39 ± 0.05 |
Spleen | 0.16 ± 0.01 | 0.08 ± 0.02 | 0.05 ± 0.01 |
Lung | 0.50 ± 0.11 | 0.30 ± 0.08 | 0.14 ± 0.04 |
Kidney | 1.64 ± 0.15 | 1.97 ± 0.21 | 1.65 ± 0.16 |
Muscle | 0.25 ± 0.06 | 0.19 ± 0.02 | 0.05 ± 0.02 |
Bone | 0.55 ± 0.15 | 0.21 ± 0.06 | 0.20 ± 0.01 |
Large Intestine | 0.39 ± 0.17 | 0.51 ± 0.04 | 1.22 ± 0.24 |
Small Intestine | 0.99 ± 0.14 | 0.56 ± 0.09 | 0.20 ± 0.05 |
Stomach | 0.15 ± 0.03 | 0.14 ± 0.07 | 0.04 ± 0.02 |
Brain | 0.02 ± 0.01 | 0.01 ± 0.01 | 0.01 ± 0.005 |
Tumor | 0.21 ± 0.07 | 0.40 ± 0.05 | 0.21 ± 0.08 |
Blood | 0.96 ± 0.23 | 0.87 ± 0.16 | 0.13 ± 0.06 |
T/M ratio | 0.84 ± 0.09 | 2.11 ± 0.18 | 4.20 ± 0.25 |
T/B ratio | 0.38 ± 0.05 | 1.90 ± 0.16 | 1.10 ± 0.08 |
3. Experimental
3.1. General Information
3.2. Synthesis
Synthesis of 99mTcN-MAG-ADMQ ([99mTcN]-1)
Synthesis of 99mTcN-MAG3- ADMQ ([99mTcN]-2)
3.3. In Vitro Stability Study
3.4. Radio-HPLC Analysis
3.5. Paper Electrophoresis
3.6. Measurement of Partition Coefficients
3.7. Biodistribution Study
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
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Zhao, M.; Ning, H.; Feng, M.; Li, S.; Chang, J.; Qi, C. Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging. Molecules 2014, 19, 5508-5521. https://doi.org/10.3390/molecules19055508
Zhao M, Ning H, Feng M, Li S, Chang J, Qi C. Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging. Molecules. 2014; 19(5):5508-5521. https://doi.org/10.3390/molecules19055508
Chicago/Turabian StyleZhao, Mingxia, Hongyu Ning, Man Feng, Shilei Li, Jin Chang, and Chuanmin Qi. 2014. "Novel [99mTcN]2+ Labeled EGFR Inhibitors as Potential Radiotracers for Single Photon Emission Computed Tomography (SPECT) Tumor Imaging" Molecules 19, no. 5: 5508-5521. https://doi.org/10.3390/molecules19055508