Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice

Abstract Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasiv...

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Main Authors: Aditya Bansal, Shalini Sharma, Benedikt Klasen, Frank Rösch, Mukesh K. Pandey
Format: Article
Language:English
Published: Nature Portfolio 2022-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-19953-4
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author Aditya Bansal
Shalini Sharma
Benedikt Klasen
Frank Rösch
Mukesh K. Pandey
author_facet Aditya Bansal
Shalini Sharma
Benedikt Klasen
Frank Rösch
Mukesh K. Pandey
author_sort Aditya Bansal
collection DOAJ
description Abstract Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasive imaging of cell trafficking offers such a potential. Herein, we evaluated and compared three different ready-to-use direct cell radiolabeling synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA for PET imaging-based trafficking of white blood cells (WBCs) and stem cells (SCs) up to 7 days in athymic nude mice. We compared the degree of 89Zr complexation and percentage of cell radiolabeling efficiencies with each. All three synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA, were successfully prepared, and used for radiolabeling of WBCs and SCs. The highest cell radiolabeling yield was found for [89Zr]Zr-DFO-Bn-NCS, followed by [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA. In terms of biodistribution, WBCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS, were primarily accumulated in liver and spleen, whereas SCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS were found in lung, liver and spleen. A high bone uptake was observed for both WBCs and SCs radiolabeled with [89Zr]Zr-Hy3ADA5-SA, suggesting in-vivo instability of [89Zr]Zr-Hy3ADA5-SA synthon. This study offers an appropriate selection of ready-to-use radiolabeling synthons for noninvasive trafficking of WBCs, SCs and other cell-based therapies.
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spelling doaj.art-a7a2496301474d7d928456833ddee2d02022-12-22T03:18:08ZengNature PortfolioScientific Reports2045-23222022-09-0112111310.1038/s41598-022-19953-4Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic miceAditya Bansal0Shalini Sharma1Benedikt Klasen2Frank Rösch3Mukesh K. Pandey4Division of Nuclear Medicine, Department of Radiology, Mayo ClinicDivision of Nuclear Medicine, Department of Radiology, Mayo ClinicDepartment of Chemistry-TRIGA Site, Johannes Gutenberg UniversityDepartment of Chemistry-TRIGA Site, Johannes Gutenberg UniversityDivision of Nuclear Medicine, Department of Radiology, Mayo ClinicAbstract Cell based therapies are evolving as an effective new approach to treat various diseases. To understand the safety, efficacy, and mechanism of action of cell-based therapies, it is imperative to follow their biodistribution noninvasively. Positron-emission-tomography (PET)-based non-invasive imaging of cell trafficking offers such a potential. Herein, we evaluated and compared three different ready-to-use direct cell radiolabeling synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA for PET imaging-based trafficking of white blood cells (WBCs) and stem cells (SCs) up to 7 days in athymic nude mice. We compared the degree of 89Zr complexation and percentage of cell radiolabeling efficiencies with each. All three synthons, [89Zr]Zr-DFO-Bn-NCS, [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA, were successfully prepared, and used for radiolabeling of WBCs and SCs. The highest cell radiolabeling yield was found for [89Zr]Zr-DFO-Bn-NCS, followed by [89Zr]Zr-Hy3ADA5-NCS, and [89Zr]Zr-Hy3ADA5-SA. In terms of biodistribution, WBCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS, were primarily accumulated in liver and spleen, whereas SCs radiolabeled with [89Zr]Zr-DFO-Bn-NCS or [89Zr]Zr-Hy3ADA5-NCS were found in lung, liver and spleen. A high bone uptake was observed for both WBCs and SCs radiolabeled with [89Zr]Zr-Hy3ADA5-SA, suggesting in-vivo instability of [89Zr]Zr-Hy3ADA5-SA synthon. This study offers an appropriate selection of ready-to-use radiolabeling synthons for noninvasive trafficking of WBCs, SCs and other cell-based therapies.https://doi.org/10.1038/s41598-022-19953-4
spellingShingle Aditya Bansal
Shalini Sharma
Benedikt Klasen
Frank Rösch
Mukesh K. Pandey
Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
Scientific Reports
title Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
title_full Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
title_fullStr Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
title_full_unstemmed Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
title_short Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
title_sort evaluation of different 89zr labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice
url https://doi.org/10.1038/s41598-022-19953-4
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