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Theranostics 2015; 5(3):227-239. doi:10.7150/thno.10185 This issue Cite

Research Paper

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

Christina M. Lewis^*1, Stephen A. Graves^*1, Reinier Hernandez¹, Hector F. Valdovinos¹, Todd E. Barnhart¹, Weibo Cai^1,2,3, Mary E. Meyerand^1,2,4, Robert J. Nickles¹, Masatoshi Suzuki^{5 ✉}

1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
2. Department of Radiology, University of Wisconsin - Madison, Madison, WI, USA;
3. Carbone Cancer Center, University of Wisconsin - Madison, Madison, WI, USA;
4. Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, USA;
5. Department of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA.
* Authors contributed equally to this work.

✉ Corresponding author: Masatoshi Suzuki, 4124 Veterinary Medicine Building, 2015 Linden Drive, Madison, WI 53706, USA. Tel: (608) 262-4264; Fax: (608) 890-3667; E-mail: msuzukivetmed.wisc.edu.

Abstract

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.

Keywords: Positron emission tomography (PET), manganese-enhanced magnetic resonance imaging (MEMRI), multimodality imaging, manganese-52 (⁵²Mn), cell tracking, reporter gene.

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