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

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 (...

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Bibliographic Details
Published in:Theranostics 2015-01, Vol.5 (3), p.227-239
Main Authors: Lewis, Christina M., Graves, Stephen A., Hernandez, Reinier, Valdovinos, Hector F., Barnhart, Todd E., Cai, Weibo, Meyerand, Mary E., Nickles, Robert J., Suzuki, Masatoshi
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
BASIC BIOLOGICAL SCIENCES
cell tracking
manganese-52 (52Mn)
manganese-enhanced magnetic resonance imaging (MEMRI)
multimodality imaging
Positron emission tomography (PET)
RADIOLOGY AND NUCLEAR MEDICINE
reporter gene
Research Paper
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Summary: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.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.10185