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Title: 52Mn Production for PET/MRI Tracking Of Human Stem Cells Expressing Divalent Metal Transporter 1 (DMT1)

Journal Article · · Theranostics
DOI:https://doi.org/10.7150/thno.10185· OSTI ID:1441141
 [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1];  [4]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Medical Physics
  2. Univ. of Wisconsin, Madison, WI (United States). Dept. of Medical Physics, and Dept. of Radiology; Univ. of Wisconsin, Madison, WI (United States). Dept. of Biomedical Engineering
  3. Univ. of Wisconsin, Madison, WI (United States). Dept. of Medical Physics, and Dept. of Radiology; Univ. of Wisconsin, Madison, WI (United States). Carbone Cancer Center
  4. Univ. of Wisconsin, Madison, WI (United States). Dept. of Comparative Biosciences

There is a growing demand for long-term in vivo stem cell imaging for assessing cell therapy techniques and guiding therapeutic decisions. This work develops the production of 52Mn and establishes proof of concept for the use of divalent metal transporter 1 (DMT1) as a positron emission tomography (PET) and magnetic resonance imaging (MRI) reporter gene for stem cell tracking in the rat brain. 52Mn was produced via proton irradiation of a natural chromium target. In a comparison of two 52Mn separation methods, solvent-solvent extraction was preferred over ion exchange chromatography because of reduced chromium impurities and higher 52Mn recovery. In vitro uptake of Mn-based PET and MRI contrast agents (52Mn2+ and Mn2+, respectively) was enhanced in DMT1 over-expressing human neural progenitor cells (hNPC-DMT1) compared to wild-type control cells (hNPC-WT). After cell transplantation in the rat striatum, increased uptake of Mn-based contrast agents in grafted hNPC-DMT1 was detected in in vivo manganese-enhanced MRI (MEMRI) and ex vivo PET and autoradiography. These initial studies indicate that this approach holds promise for dual-modality PET/MR tracking of transplanted stem cells in the central nervous system and prompt further investigation into the clinical applicability of this technique.

Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH); National Science Foundation (NSF)
Grant/Contract Number:
SC0008384
OSTI ID:
1441141
Journal Information:
Theranostics, Vol. 5, Issue 3; ISSN 1838-7640
Publisher:
IvyspringCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 61 works
Citation information provided by
Web of Science

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Nanomaterials in Neural-Stem-Cell-Mediated Regenerative Medicine: Imaging and Treatment of Neurological Diseases journal March 2018
New imaging probes to track cell fate: reporter genes in stem cell research journal July 2017
Lost signature: progress and failures in in vivo tracking of implanted stem cells journal September 2015
Manganese-52: applications in cell radiolabelling and liposomal nanomedicine PET imaging using oxine (8-hydroxyquinoline) as an ionophore journal January 2018
52g/55 Mn-Labelled CDTA-based trimeric complexes as novel bimodal PET/MR probes with high relaxivity journal January 2019
Cancer stem cells in radiation response: current views and future perspectives in radiation oncology journal March 2019
Stem Cell Tracking Technologies for Neurological Regenerative Medicine Purposes journal January 2017
Non-invasive in vivo imaging of cardiac stem/progenitor cell biodistribution and retention after intracoronary and intramyocardial delivery in a swine model of chronic ischemia reperfusion injury journal March 2017
Cellular magnetic resonance imaging contrast generated by the ferritin heavy chain genetic reporter under the control of a Tet-On switch journal October 2015
Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration journal December 2018
Perspectives on the Use of Liquid Extraction for Radioisotope Purification journal January 2019
Pre- and postmortem imaging of transplanted cells journal September 2015
Cell Tracking in Cancer Immunotherapy journal February 2020
An Overview of Multimodal Neuroimaging Using Nanoprobes journal February 2017
Enzyme-Controlled Intracellular Self-Assembly of 18F Nanoparticles for Enhanced MicroPET Imaging of Tumor journal January 2015
Nanoparticle-based Cell Trackers for Biomedical Applications journal January 2020