Tumor Uptake of Triazine Dendrimers Decorated with Four, Sixteen, and Sixty-Four PSMA-Targeted Ligands: Passive versus Active Tumor Targeting
Abstract
:1. Introduction
2. Materials and Methods
2.1. General Procedures
2.2. Synthesis
2.3. Cell Lines and Animal Models
2.4. Preparation of 64Cu-Labeld G1-(DUPA)4, G3-(DUPA)16, and G5-(DUPA)64
2.5. Serum Stability Assay
2.6. Competition Assay
2.7. Cell Uptake and Internalization
2.8. Small Animal PET/CT Imaging
3. Results and Discussion
3.1. Synthesis and Characterization of G1-(DUPA)4, G3-(DUPA)16, and G5-(DUPA)64
3.2. Radiolabeling and Serum Stability
3.3. In Vitro Cell Assays
3.4. PET/CT Imaging in Mouse Models
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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G1-(DUPA)4 | G3-(DUPA)16 | G5-(DUPA)64 | |||||||
---|---|---|---|---|---|---|---|---|---|
1 h p.i. | 4 h p.i. | 24 h p.i. | 1 h p.i. | 4 h. p.i. | 24 h. p.i. | 1 h p.i. | 4 h. p.i. | 24 h. p.i. | |
Brain | 0.03 ± 0.01 | 0.02 ± 0.00 | 0.07 ± 0.00 | 0.04 ± 0.01 | 0.04 ± 0.01 | 0.07 ± 0.03 | 0.94 ± 0.10 | 0.66 ± 0.08 | 0.20 ± 0.06 |
Heart | 0.16 ± 0.05 | 0.10 ± 0.02 | 0.25 ± 0.05 | 0.20 ± 0.03 | 0.17 ± 0.03 | 0.29 ± 0.03 | 15.37 ± 1.46 | 10.77 ± 1.55 | 1.60 ± 0.10 |
Liver | 1.03 ± 0.16 | 1.20 ± 0.20 | 1.93 ± 0.15 | 1.23 ± 0.21 | 1.45 ± 0.13 | 2,20 ± 0.27 | 11.43 ± 1.27 | 13.67 ± 0.97 | 18.90 ± 1.04 |
Left Kidney | 53.27 ± 4.37 | 58.73 ± 4.98 | 54.00 ± 5.96 | 42.85 ± 3.43 | 45.00 ± 4.63 | 43.85 ± 5.13 | 6.10 ± 1.57 | 5.47 ± 0.76 | 2.93 ± 0.59 |
Right Kidney | 56.83 ± 5.14 | 59.97 ± 3.27 | 55.03 ± 7.36 | 44.28 ± 4.79 | 48.55 ± 6.59 | 46.95 ± 6.35 | 6.23 ± 0.29 | 5.73 ± 0.51 | 3.17 ± 0.45 |
Muscle | 0.06 ± 0.03 | 0.05 ± 0.01 | 0.13 ± 0.03 | 0.20 ± 0.04 | 0.18 ± 0.02 | 0.23 ± 0.03 | 0.49 ± 0.07 | 0.42 ± 0.06 | 0.29 ± 0.06 |
Bone | 0.08 ± 0.03 | 0.07 ± 0.01 | 0.08 ± 0.02 | 0.27 ± 0.08 | 0.22 ± 0.03 | 0.27 ± 0.08 | 0.93 ± 0.04 | 0.90 ± 0.17 | 0.98 ± 0.20 |
PC3-PIP | 0.99 ± 0.36 | 0.87 ± 0.40 | 0.81 ± 0.36 | 0.66 ± 0.15 | 0.64 ± 0.11 | 0.67 ± 0.08 | 0.97 ± 0.03 | 1.57 ± 0.15 | 1.83 ± 0.21 |
PC3-FLU | 0.18 ± 0.05 | 0.13 ± 0.02 | 0.33 ± 0.06 | 0.45 ± 0.06 | 0.42 ± 0.05 | 0.54 ± 0.08 | 1.16 ± 0.21 | 1.83 ± 0.32 | 1.97 ± 0.31 |
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Lim, J.; Guan, B.; Nham, K.; Hao, G.; Sun, X.; Simanek, E.E. Tumor Uptake of Triazine Dendrimers Decorated with Four, Sixteen, and Sixty-Four PSMA-Targeted Ligands: Passive versus Active Tumor Targeting. Biomolecules 2019, 9, 421. https://doi.org/10.3390/biom9090421
Lim J, Guan B, Nham K, Hao G, Sun X, Simanek EE. Tumor Uptake of Triazine Dendrimers Decorated with Four, Sixteen, and Sixty-Four PSMA-Targeted Ligands: Passive versus Active Tumor Targeting. Biomolecules. 2019; 9(9):421. https://doi.org/10.3390/biom9090421
Chicago/Turabian StyleLim, Jongdoo, Bing Guan, Kien Nham, Guiyang Hao, Xiankai Sun, and Eric E. Simanek. 2019. "Tumor Uptake of Triazine Dendrimers Decorated with Four, Sixteen, and Sixty-Four PSMA-Targeted Ligands: Passive versus Active Tumor Targeting" Biomolecules 9, no. 9: 421. https://doi.org/10.3390/biom9090421