[ 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 [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.

Keywords: Cardiopoietic stem cells; Imaging; Myocardial infarction; Positron-emission tomography; Radiolabeling; Regenerative medicine.