[89Zr]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 [89Zr]zirconium-p-isothiocyanatobenzyl-desferrioxamine ([89Zr]Zr-DBN) labeled human cardiopoietic stem cells (CPs) were evaluated in a model of ischemic heart failure. Methods and results [89Zr]Zr-DBN based radiolabeling of human CPs yielded [89Zr]Zr-DBN-CPs with radioactivity yield of 0.70 ± 0.20 MBq/106 cells and excellent label stability. Compared to unlabeled cell counterparts, [89Zr]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, [89Zr]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 [89Zr]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.