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 - Funding Information:
The authors thank Lois Rowe and Ryan Mahlberg for histology, and Paul G. Stalboerger and Jilian L. Foxen for project management. Authors were supported by NIH 5R21HL127389-02, NIH 4T32HL007111-39, NIH R01HL134664, Mayo Clinic Department of Radiology, Accelerated Regenerative Medicine Award, Mayo Clinic Center for Regenerative Medicine, Van Cleve Cardiac Regenerative Medicine Program, Marriott Foundation, and Michael S. and Mary Sue Shannon Family. S.Y. A. Behfar, and A.T. are co-inventors on regenerative sciences related intellectual property disclosed to Mayo Clinic. A. Bansal. M.P. and T.D. are co-inventors on 89Zr related intellectual property disclosed to Mayo Clinic. Previously, Mayo Clinic has administered research grants from Celyad. Mayo Clinic, A. Behfar, and A.T. have interests in Rion LLC.
Funding Information:
The authors thank Lois Rowe and Ryan Mahlberg for histology, and Paul G. Stalboerger and Jilian L. Foxen for project management. Authors were supported by NIH 5R21HL127389-02 , NIH 4T32HL007111-39 , NIH R01HL134664 , Mayo Clinic Department of Radiology , Accelerated Regenerative Medicine Award , Mayo Clinic Center for Regenerative Medicine , Van Cleve Cardiac Regenerative Medicine Program , Marriott Foundation , and Michael S. and Mary Sue Shannon Family .
Funding Information:
S.Y., A. Behfar, and A.T. are co-inventors on regenerative sciences related intellectual property disclosed to Mayo Clinic. A. Bansal., M.P., and T.D. are co-inventors on 89 Zr related intellectual property disclosed to Mayo Clinic. Previously, Mayo Clinic has administered research grants from Celyad. Mayo Clinic, A. Behfar, and A.T. have interests in Rion LLC.
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 - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
ER -