Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging
Abstract
:1. Introduction
2. Materials and Methods
2.1. Production of Endothelial LEVs
2.2. Purification and Characterization of LEVs
2.2.1. Purification
2.2.2. Flow Cytometry
2.2.3. Tunable Resistive Pulse Sensing (TRPS)
2.2.4. Transmission Electron Microscopy (TEM)
2.2.5. Western Blot Analysis
2.3. Radiolabeling of LEVs
2.4. Purification of Radiolabeled LEVs from Free [99mTc]Tc-AnnV Radiotracer
2.5. Stability of Radiolabeled LEVs in Serum
2.6. In Vivo Experimentations
2.7. Mouse Model of Hind Limb Ischemia Induction and Follow-Up
2.8. Quantification of the In Vivo Biodistribution of Radiolabeled LEVs by Isotopic Imaging
2.9. Statistical Analysis
3. Results
3.1. Characterization of Produced Endothelial LEVs
3.2. Endothelial LEVs Were Successfully Radiolabeled and Purified
3.3. Endothelial LEVs Preferentially Homed to the Ischemic Hind Limb
3.4. Tracking of LEV Homing Correlated with Therapeutic Effects
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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%ID/mm3 | Liver | Kidneys | Heart | Lungs | Spleen | Brain | Ipsi Hind Limb | Contra Hind Limb |
---|---|---|---|---|---|---|---|---|
free [99mTc]Tc-AnnV (n = 3) | 0.51 ± 0.10 | 7.78 ± 0.79 | 0.16 ± 0.07 | 0.23 ± 0.02 | 0.20 ± 0.14 | 0.05 ± 0.04 | 0.09 ± 0.02 € | 0.13 ± 0.05 € |
[99mTc]Tc-AnnV-LEVs (n = 10) | 9.81 ± 1.83 | 2.99 ± 1.60 | 0.67 ± 0.19 | 0.97 ± 0.36 | 2.04 ± 1.05 | 0.16 ± 0.14 | 0.41 ± 0.09 ¥ | 0.23 ± 0.06 ¥ |
Post-hoctest p value | **** <0.0001 | *** 0.0010 | *** 0.0003 | *** 0.0005 | ** 0.0019 | ns 0.2957 | ** 0.0013 | ns 0.4958 |
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Giraud, R.; Moyon, A.; Simoncini, S.; Duchez, A.-C.; Nail, V.; Chareyre, C.; Bouhlel, A.; Balasse, L.; Fernandez, S.; Vallier, L.; et al. Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging. Pharmaceutics 2022, 14, 121. https://doi.org/10.3390/pharmaceutics14010121
Giraud R, Moyon A, Simoncini S, Duchez A-C, Nail V, Chareyre C, Bouhlel A, Balasse L, Fernandez S, Vallier L, et al. Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging. Pharmaceutics. 2022; 14(1):121. https://doi.org/10.3390/pharmaceutics14010121
Chicago/Turabian StyleGiraud, Romain, Anaïs Moyon, Stéphanie Simoncini, Anne-Claire Duchez, Vincent Nail, Corinne Chareyre, Ahlem Bouhlel, Laure Balasse, Samantha Fernandez, Loris Vallier, and et al. 2022. "Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging" Pharmaceutics 14, no. 1: 121. https://doi.org/10.3390/pharmaceutics14010121
APA StyleGiraud, R., Moyon, A., Simoncini, S., Duchez, A.-C., Nail, V., Chareyre, C., Bouhlel, A., Balasse, L., Fernandez, S., Vallier, L., Hache, G., Sabatier, F., Dignat-George, F., Lacroix, R., Guillet, B., & Garrigue, P. (2022). Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging. Pharmaceutics, 14(1), 121. https://doi.org/10.3390/pharmaceutics14010121