Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors
Abstract
:1. Introduction
2. Results
2.1. Radiolabelling and Quality Control
2.2. Cell Uptake Studies
Comparative Cell Uptake of [99mTc]Tc–DT1 in AsPC-1, PANC-1, MiaCapa-2, and Capan-1 Cells
2.3. In Vivo Studies
2.3.1. Comparative Stability of [99mTc]Tc–DT1 and [99mTc]Tc–DT5 in Mice: The Impact of Protease Inhibitors
2.3.2. Biodistribution of [99mTc]Tc–DT1 in AsPC-1 Tumor-Bearing SCID Mice: The Impact of Protease Inhibitors
3. Discussion
4. Materials and Methods
4.1. Chemicals and Radionuclides
4.1.1. Radiolabeling
4.1.2. Quality Control
4.2. In Vitro Assays
4.2.1. Cell Lines and Culture
4.2.2. Internalization of [99mTc]Tc Radiotracers in AsPC-1, PANC-1, MiaCapa-2, and Capan-1 Cells
4.3. Animal Studies
4.3.1. Metabolic Studies in Mice
4.3.2. Tumor Induction in SCID Mice
4.3.3. Biodistribution in SCID Mice Bearing AsPC-1 and MiaCapa-2 Xenografts
4.3.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Control | Entresto | Lis | Entresto+Lis | |
---|---|---|---|---|
[99mTc]Tc–DT1 | 1.8 ± 0.8 (n = 4) | 5.5 ± 3.9 (n = 5) | 18.8 ± 2.5 (n = 3) | 63.8 ± 7.5 (n = 3) |
[99mTc]Tc–DT5 | 1.2 ± 0.2 (n = 3) | 2.0 ± 0.6 (n = 3) | 28.7 ± 3.6 (n = 3) | 70.2 ± 4.9 (n = 3) |
[99mTc]Tc–DT1: 4 h pi | |||||
---|---|---|---|---|---|
Controls 1 | Entresto + Lis 2 | Block 3 | |||
Blood | 0.07 ± 0.01 | 0.08 ± 0.02 | 0.09 ± 0.01 | ||
Liver | 0.44 ± 0.05 | 0.67 ± 0.06 | 0.55 ± 0.06 | ||
Heart | 0.08 ± 0.01 | 0.11 ± 0.02 | 0.18 ± 0.11 | ||
Kidneys | 4.18 ± 3.80 | ⇤ p < 0.0001 ⇥ | 6.81 ± 1.74 | ⇤ p < 0.001 ⇥ | 4.15 ± 1.75 |
Stomach | 0.48 ± 0.26 | 0.57 ± 0.14 | 2.75 ± 1.63 | ||
Intestines | 0.65 ± 0.04 | 2.13 ± 0.24 | 1.07 ± 0.01 | ||
Spleen | 0.22 ± 0.05 | 0.58 ± 0.35 | 0.31 ± 0.07 | ||
Muscle | 0.03 ± 0.01 | 0.06 ± 0.03 | 0.07 ± 0.06 | ||
Lungs | 0.18 ± 0.03 | 0.62 ± 0.35 | 0.41 ± 0.07 | ||
Pancreas | 0.05 ± 0.01 | 0.10 ± 0.01 | 0.08 ± 0.00 | ||
Tumor | 1.25 ± 0.14 | ⇤ p < 0.0001 ⇥ | 7.05 ± 0.80 | ⇤ p < 0.0001 ⇥ | 0.74 ± 0.01 |
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Kanellopoulos, P.; Nock, B.A.; Krenning, E.P.; Maina, T. Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors. Int. J. Mol. Sci. 2020, 21, 7926. https://doi.org/10.3390/ijms21217926
Kanellopoulos P, Nock BA, Krenning EP, Maina T. Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors. International Journal of Molecular Sciences. 2020; 21(21):7926. https://doi.org/10.3390/ijms21217926
Chicago/Turabian StyleKanellopoulos, Panagiotis, Berthold A. Nock, Eric P. Krenning, and Theodosia Maina. 2020. "Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors" International Journal of Molecular Sciences 21, no. 21: 7926. https://doi.org/10.3390/ijms21217926