225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis and Chemical Characterization of HEHA-HYNIC-iPSMA-RGD (iPSMA-RGD)
2.2. Preparation of 225Ac-iPSMA-RGD
2.3. In Vitro Evaluation of 225Ac-iPSMA-RGD
2.3.1. Stability in Saline Solution (0.9% NaCl) and Human Serum
2.3.2. Cellular Uptake, Internalization, and Viability
2.3.3. Proliferation Capability Assay
2.3.4. Apoptosis
2.3.5. Oxidative Stress
2.3.6. Double-Stranded DNA Breaks
2.4. In Vivo Assessment
2.4.1. Biodistribution and Biokinetics
2.4.2. Ex-Vivo Imaging
3. Materials and Methods
3.1. Conjugation of HYNIC-iPSMA-RGD to HEHA-SCN
3.2. Spectroscopic Characterization by FT-IR and UV-Vis Characterization
3.3. Mass Spectrometry Characterization
3.4. Radiolabeling and Radiochemical Purity Evaluation
3.5. Serum Stability
3.6. Cell Culture
3.7. Uptake and Internalization in Cells
3.8. Cytotoxicity after 225Ac-iPSMA-RGD Treatment
3.9. Proliferation Capability Assay
3.10. Apoptosis
3.11. Reactive Oxygen Species
3.12. DNA Double-Stranded Breaks Assay
3.13. Biodistribution
3.14. Absorbed Radiation Dose Estimation
3.15. Histology and Immunohistochemistry Protocol
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
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Organ | 225Ac-iPSMA | 225Ac-RGD | 225Ac-iPSMA-RGD | |||
---|---|---|---|---|---|---|
Radiation Absorbed Dose Gy/37 kBq | Radiation Absorbed Dose Gy/37 kBq | Radiation Absorbed Dose Gy/37 kBq | ||||
Kidney | 4.41 | 22.04 | 1.78 | 8.90 | 3.52 | 17.63 |
Liver | 2.10 | 6.38 | 3.92 | 11.89 | 5.23 | 15.85 |
Tumor | 6.04 | 182.87 | 1.72 | 51.92 | 7.83 | 237.07 |
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Ocampo-García, B.; Cruz-Nova, P.; Jiménez-Mancilla, N.; Luna-Gutiérrez, M.; Oros-Pantoja, R.; Lara-Almazán, N.; Pérez-Velasco, D.; Santos-Cuevas, C.; Ferro-Flores, G. 225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins. Int. J. Mol. Sci. 2023, 24, 16553. https://doi.org/10.3390/ijms242316553
Ocampo-García B, Cruz-Nova P, Jiménez-Mancilla N, Luna-Gutiérrez M, Oros-Pantoja R, Lara-Almazán N, Pérez-Velasco D, Santos-Cuevas C, Ferro-Flores G. 225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins. International Journal of Molecular Sciences. 2023; 24(23):16553. https://doi.org/10.3390/ijms242316553
Chicago/Turabian StyleOcampo-García, Blanca, Pedro Cruz-Nova, Nallely Jiménez-Mancilla, Myrna Luna-Gutiérrez, Rigoberto Oros-Pantoja, Nancy Lara-Almazán, Diana Pérez-Velasco, Clara Santos-Cuevas, and Guillermina Ferro-Flores. 2023. "225Ac-iPSMA-RGD for Alpha-Therapy Dual Targeting of Stromal/Tumor Cell PSMA and Integrins" International Journal of Molecular Sciences 24, no. 23: 16553. https://doi.org/10.3390/ijms242316553