Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Radioligands
2.1.1. Peptides and Protease Inhibitors
2.1.2. Radiolabeling–Quality Control
2.2. Cell Studies
2.2.1. Cell Culture
2.2.2. Uptake/Internalization of [99mTc]Tc-DT11 in PC-3 Cells
2.2.3. Uptake/Internalization of [99mTc]Tc-DT11+[99mTc]Tc-DB7 in PC-3 Cells
2.3. Animal Studies
2.3.1. Metabolic Stability in Mice
2.3.2. Biodistribution of [99mTc]Tc-DT11 in PC-3 Tumor-Bearing Mice
2.3.3. Biodistribution of [99mTc]Tc-DT11+[99mTc]Tc-DB7 in PC-3 Tumor-Bearing Mice
2.3.4. SPECT/CT of [99mTc]Tc-DT11+[99mTc]Tc-DB7 in PC-3 Tumor-Bearing Mice
3. Results
3.1. Ligands and Radioligands
3.2. In Vitro Assays in PC-3 Cells
3.3. Metabolic Stability
3.4. Biodistribution in PC-3 Tumor-Bearing Mice
3.4.1. Biodistribution of [99mTc]Tc-DT11
3.4.2. Biodistribution of [99mTc]Tc-DT11+[99mTc]Tc-DB7 in PC-3 Tumor-Bearing Mice
3.4.3. SPECT/CT of [99mTc]Tc-DT11+[99mTc]Tc-DB7 in PC-3 Tumor-Bearing Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Mixture 1 | +[Tyr4]BBN 2 | +NT 3 | +[Tyr4]BBN + NT | ||
---|---|---|---|---|---|
total/block | membrane-bound | 7.04 ± 0.55 | 1.63 ± 0.13 | 7.91 ± 0.39 | 1.50 ± 0.10 |
internalized | 3.70 ± 0.33 | 2.73 ± 0.46 | 2.26 ± 0.13 | 1.17 ± 0.15 | |
sum | 10.74 ± 0.61 | 4.36 ± 0.51 | 10.16 ± 0.45 | 2.67 ± 0.21 | |
specific | membrane-bound | 5.54 ± 0.52 4 | 0.19 ± 0.15 5 | 6.40 ± 0.34 6 | - |
internalized | 2.54 ± 0.32 | 1.68 ± 0.49 | 1.09 ± 0.26 | - | |
sum | 8.08 ± 0.62 | 1.87 ± 0.56 | 7.49 ± 0.46 | - |
[99mTc]Tc-DT11 * | [99mTc]Tc-DB7 | |
---|---|---|
Control | 56.56 ± 5.19% | 70.6 ± 1.1% * |
Entresto® | 76.98 ± 3.31% | 93.7 ± 2.2% |
PA | - | 94.5 ± 1.1% * |
Organs/Tissues | Block (n = 3) 1,2 | Controls (n = 4) 1 | Entresto® (n = 4) 1,3 |
---|---|---|---|
Blood | 0.52 ± 0.13 | 1.05 ± 0.30 | 0.53 ± 0.17 |
Liver | 1.73 ± 0.13 | 1.39 ± 0.38 | 1.37 ± 0.24 |
Heart | 0.21 ± 0.03 | 0.39 ± 0.18 | 0.17 ± 0.13 |
Kidneys | 0.23 ± 0.17 | 2.87 ± 0.37 | 3.21 ± 0.62 |
Stomach | 0.35 ± 0.20 | 0.38 ± 0.16 | 0.52 ± 0.20 |
Intestines | 1.62 ± 0.52 | 1.91 ± 0.30 | 2.79 ± 0.62 |
Spleen | 0.99 ± 0.30 | 0.89 ± 0.23 | 1.27 ± 0.39 |
Muscle | 0.09 ± 0.03 | 0.16 ± 0.09 | 0.12 ± 0.03 |
Lungs | 0.76 ± 0.15 | 1.03 ± 0.42 | 1.02 ± 1.17 |
Pancreas | 0.14 ± 0.02 | 0.26 ± 0.09 | 0.21 ± 0.03 |
PC-3 Tumor | 1.56 ± 0.43 | 4.23 ± 0.58 | 5.88 ± 1.47 |
Organs/Tissues | Controls | Entresto® 1 | Block 1 2 | Block 2 3 | Block 3 4 |
---|---|---|---|---|---|
Blood | 1.01 ± 0.29 | 0.72 ± 0.13 | 1.08 ± 0.13 | 1.64 ± 0.52 | 1.41 ± 0.92 |
Liver | 1.27 ± 0.18 | 1.09 ± 0.15 | 1.37 ± 0.08 | 1.81 ± 0.45 | 1.88 ± 0.44 |
Heart | 0.44 ± 0.11 | 0.30 ± 0.12 | 0.39 ± 0.13 | 0.52 ± 0.19 | 0.63 ± 0.53 |
Kidneys | 2.69 ± 0.25 | 2.83 ± 0.53 | 2.78 ± 0.30 | 2.93 ± 0.62 | 3.12 ± 0.97 |
Stomach | 0.58 ± 0.19 | 0.51 ± 0.22 | 0.52 ± 0.12 | 0.67 ± 0.30 | 0.71 ± 0.13 |
Intestines | 1.68 ± 0.13 | 1.98 ± 0.35 | 1.40 ± 0.17 | 1.96 ± 0.08 | 1.71 ± 0.36 |
Spleen | 0.67 ± 0.12 | 0.73 ± 0.10 | 0.76 ± 0.07 | 0.98 ± 0.20 | 0.80 ± 0.17 |
Muscle | 0.14 ± 0.04 | 0.12 ± 0.02 | 0.15 ± 0.02 | 0.22 ± 0.10 | 0.18 ± 0.11 |
Lungs | 0.80 ± 0.15 | 0.93 ± 0.17 | 0.89 ± 0.10 | 1.33 ± 0.35 | 1.65 ± 1.02 |
Pancreas | 0.55 ± 0.08 | 0.77 ± 0.09 | 0.60 ± 0.03 | 0.50 ± 0.10 | 0.45 ± 0.10 |
PC-3 Tumor | 7.70 ± 0.89 | 11.57 ± 1.92 | 7.28 ± 1.00 | 3.57 ± 0.44 | 2.05 ± 0.53 |
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Share and Cite
Bibika, M.; Kanellopoulos, P.; Rouchota, M.; Loudos, G.; Nock, B.A.; Krenning, E.P.; Maina, T. Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results. Pharmaceutics 2024, 16, 1223. https://doi.org/10.3390/pharmaceutics16091223
Bibika M, Kanellopoulos P, Rouchota M, Loudos G, Nock BA, Krenning EP, Maina T. Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results. Pharmaceutics. 2024; 16(9):1223. https://doi.org/10.3390/pharmaceutics16091223
Chicago/Turabian StyleBibika, Maria, Panagiotis Kanellopoulos, Maritina Rouchota, George Loudos, Berthold A. Nock, Eric P. Krenning, and Theodosia Maina. 2024. "Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results" Pharmaceutics 16, no. 9: 1223. https://doi.org/10.3390/pharmaceutics16091223
APA StyleBibika, M., Kanellopoulos, P., Rouchota, M., Loudos, G., Nock, B. A., Krenning, E. P., & Maina, T. (2024). Diagnosis of Prostate Cancer with a Neurotensin–Bombesin Radioligand Combination—First Preclinical Results. Pharmaceutics, 16(9), 1223. https://doi.org/10.3390/pharmaceutics16091223