[(89)Zr]Zr-DBN labeled cardiopoietic stem cells proficient for heart failure.

INTRODUCTION: Radiolabeling of stem cells with a positron emitting radioisotope represents a major advancement in regenerative biotherapy enabling non-invasive imaging. To assess the value of such an approach in a clinically relevant scenario, the tolerability and therapeutic aptitude of [(89)Zr]zirconium-p-isothiocyanatobenzyl-desferrioxamine ([(89)Zr]Zr-DBN) labeled human cardiopoietic stem cells (CPs) were evaluated in a model of ischemic heart failure. METHODS AND RESULTS: [(89)Zr]Zr-DBN based radiolabeling of human CPs yielded [(89)Zr]Zr-DBN-CPs with radioactivity yield of 0.70 ± 0.20 MBq/10(6) cells and excellent label stability. Compared to unlabeled cell counterparts, [(89)Zr]Zr-DBN-CPs maintained morphology, viability, and proliferation capacity with characteristic expression of mesodermal and pro-cardiogenic transcription factors defining the cardiopoietic phenotype. Administered in chronically infarcted murine hearts, [(89)Zr]Zr-DBN-CPs salvaged cardiac pump failure, documented by improved left ventricular ejection fraction not inferior to unlabeled CPs and notably superior to infarcted hearts without cell treatment. CONCLUSION: The present study establishes that [(89)Zr]Zr-DBN labeling does not compromise stem cell identity or efficacy in the setting of heart failure, offering a non-invasive molecular imaging platform to monitor regenerative biotherapeutics post-transplantation.