TY - JOUR
T1 - [89Zr]Zr-DBN labeled cardiopoietic stem cells proficient for heart failure
AU - Bansal, Aditya
AU - Pandey, Mukesh K.
AU - Yamada, Satsuki
AU - Goyal, Ribu
AU - Schmit, Nicholas R.
AU - Jeon, Ryounghoon
AU - Nesbitt, Jonathan J.
AU - Witt, Tyra A.
AU - Singh, Raman D.
AU - Gunderson, Tina M.
AU - Boroumand, Soulmaz
AU - Li, Mark
AU - Crespo-Diaz, Ruben J.
AU - Hillestad, Matthew L.
AU - Terzic, Andre
AU - Behfar, Atta
AU - DeGrado, Timothy R.
N1 - Publisher Copyright:
© 2020
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - Cardiopoietic stem cells
KW - Imaging
KW - Myocardial infarction
KW - Positron-emission tomography
KW - Radiolabeling
KW - Regenerative medicine
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U2 - 10.1016/j.nucmedbio.2020.09.001
DO - 10.1016/j.nucmedbio.2020.09.001
M3 - Article
C2 - 32957056
AN - SCOPUS:85091074477
SN - 0969-8051
VL - 90-91
SP - 23
EP - 30
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
ER -