Aditya Bansal1, Mukesh K Pandey2, Satsuki Yamada3, Ribu Goyal2, Nicholas R Schmit2, Ryounghoon Jeon4, Jonathan J Nesbitt4, Tyra A Witt4, Raman D Singh4, Tina M Gunderson5, Soulmaz Boroumand4, Mark Li4, Ruben J Crespo-Diaz4, Matthew L Hillestad4, Andre Terzic6, Atta Behfar7, Timothy R DeGrado8. 1. Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: Bansal.Aditya@mayo.edu. 2. Department of Radiology, Mayo Clinic, Rochester, MN, USA. 3. Center for Regenerative Medicine, Van Cleve Cardiac Regenerative Medicine Program, Marriott Heart Disease Research Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, USA. 4. Center for Regenerative Medicine, Van Cleve Cardiac Regenerative Medicine Program, Marriott Heart Disease Research Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. 5. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. 6. Center for Regenerative Medicine, Van Cleve Cardiac Regenerative Medicine Program, Marriott Heart Disease Research Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Clinical Genomics, Mayo Clinic, Rochester, MN, USA. 7. Center for Regenerative Medicine, Van Cleve Cardiac Regenerative Medicine Program, Marriott Heart Disease Research Program, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. 8. Department of Radiology, Mayo Clinic, Rochester, MN, USA. Electronic address: DeGrado.Timothy@mayo.edu.
Abstract
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.
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 humanCPs 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.
Authors: Mukesh K Pandey; Aditya Bansal; Jason R Ellinghuysen; Daniel J Vail; Heather M Berg; Timothy R DeGrado Journal: Am J Nucl Med Mol Imaging Date: 2022-02-15
Authors: Massis Krekorian; Kimberley R G Cortenbach; Milou Boswinkel; Annemarie Kip; Gerben M Franssen; Andor Veltien; Tom W J Scheenen; René Raavé; Nicolaas Koen van Riessen; Mangala Srinivas; Ingrid Jolanda M de Vries; Carl G Figdor; Erik H J G Aarntzen; Sandra Heskamp Journal: Cancers (Basel) Date: 2021-10-10 Impact factor: 6.575