Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging

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Giraud, Romain | Moyon, Anaïs | Simoncini, Stéphanie | Duchez, Anne-Claire | Nail, Vincent | Chareyre, Corinne | Bouhlel, Ahlem | Balasse, Laure | Fernandez, Samantha | Vallier, Loris | Hache, Guillaume | Sabatier, Florence | Dignat-George, Françoise | Lacroix, Romaric | Guillet, Benjamin | Garrigue, Philippe

Edité par CCSD ; MDPI -

International audience. Microvesicles, so-called endothelial large extracellular vesicles (LEVs), are of great interest as biological markers and cell-free biotherapies in cardiovascular and oncologic diseases. However, their therapeutic perspectives remain limited due to the lack of reliable data regarding their systemic biodistribution after intravenous administration. Methods: Applied to a mouse model of peripheral ischemia, radiolabeled endothelial LEVs were tracked and their in vivo whole-body distribution was quantified by microSPECT/CT imaging. Hindlimb perfusion was followed by LASER Doppler and motility impairment function was evaluated up to day 28 post-ischemia. Results: Early and specific homing of LEVs to ischemic hind limbs was quantified on the day of ischemia and positively correlated with reperfusion intensity at a later stage on day 28 after ischemia, associated with an improved motility function. Conclusions: This concept is a major asset for investigating the biodistribution of LEVs issued from other cell types, including cancer, thus partly contributing to better knowledge and understanding of their fate after injection.

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