Development of INER-PP-F11N as the Peptide-Radionuclide Conjugate Drug Against CCK2 Receptor-Overexpressing Tumors
Abstract
1. Introduction
2. Results
2.1. Structural Designs of Various CCK2R Derivatives Between DOTA and the C-Terminal Binding Sequence
2.2. Radiolabeling DOTA-CCK2R Derivatives Revealed High Efficiency and Reliable Stability
2.3. Lu-177-Labeled DOTA-CCK2R Derivatives Revealed High Cellular Binding and Internalization in A431-CCK2R (+) but Not A431-CCK2R (−) Cells
2.4. NanoSPECT/CT Imaging of Tumor-Bearing Mice and Biodistribution of Radiotracers
2.5. Mice Receiving Lu-177-Labeled DOTA-CCK2R Derivative Therapy Generated Potent Anti-Tumor Effects
2.6. Histopathological Examination of the Mice After Radiolabeled Drug Administration
3. Discussion
4. Materials and Methods
4.1. Reagents and Cell Lines
4.2. Radioisotope Labeling of CCK2R Analogs
4.3. Metabolic Stability Analysis
4.4. Analysis of In Vitro Binding and Internalization Assay
4.5. Animal Tumor Model
4.6. NanoSPECT/CT Imaging
4.7. Biodistribution Study
4.8. Therapeutic Responses to Lu-177-Labeled CCK2R Analogs in CCK2R-Expressing Cancer-Bearing Mice
4.9. Histopathological Examinations
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CCK2R | Cholecystokinin receptor subtype 2 |
DOTA | 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid |
PP-F11 | (DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 |
PP-F11N | (DGlu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 |
DOTA-PP-F11N | DOTA-(Glu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 |
DOTA-INER-PP-F11N-1 | DOTA-Lys(-4-TBA)-6-AMBA-(Glu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 |
DOTA-INER-PP-F11N-2 | DOTA-Lys(-4-TBA)-AHA-(Glu)6-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH2 |
In-111 | Indium-111 |
Lu-177 | Lutetium-177 |
ITLC | instant thin-layer chromatography |
HPLC | high-performance liquid chromatography |
OS | overall survival |
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Chang, M.-C.; Chen, C.-T.; Chiang, P.-F.; Tang, I.-C.; Peng, C.-L.; Wang, Y.-F.; Tai, Y.-J.; Chiang, Y.-C. Development of INER-PP-F11N as the Peptide-Radionuclide Conjugate Drug Against CCK2 Receptor-Overexpressing Tumors. Int. J. Mol. Sci. 2025, 26, 6565. https://doi.org/10.3390/ijms26146565
Chang M-C, Chen C-T, Chiang P-F, Tang I-C, Peng C-L, Wang Y-F, Tai Y-J, Chiang Y-C. Development of INER-PP-F11N as the Peptide-Radionuclide Conjugate Drug Against CCK2 Receptor-Overexpressing Tumors. International Journal of Molecular Sciences. 2025; 26(14):6565. https://doi.org/10.3390/ijms26146565
Chicago/Turabian StyleChang, Ming-Cheng, Chun-Tang Chen, Ping-Fang Chiang, I-Chung Tang, Cheng-Liang Peng, Yuh-Feng Wang, Yi-Jou Tai, and Ying-Cheng Chiang. 2025. "Development of INER-PP-F11N as the Peptide-Radionuclide Conjugate Drug Against CCK2 Receptor-Overexpressing Tumors" International Journal of Molecular Sciences 26, no. 14: 6565. https://doi.org/10.3390/ijms26146565
APA StyleChang, M.-C., Chen, C.-T., Chiang, P.-F., Tang, I.-C., Peng, C.-L., Wang, Y.-F., Tai, Y.-J., & Chiang, Y.-C. (2025). Development of INER-PP-F11N as the Peptide-Radionuclide Conjugate Drug Against CCK2 Receptor-Overexpressing Tumors. International Journal of Molecular Sciences, 26(14), 6565. https://doi.org/10.3390/ijms26146565