title: ⁵²Mn production for PET/MRI tracking of human stem cells expressing divalent metal transporter 1 (DMT1).
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 (52)Mn 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. (52)Mn was produced via proton irradiation of a natural chromium target. In a comparison of two (52)Mn separation methods, solvent-solvent extraction was preferred over ion exchange chromatography because of reduced chromium impurities and higher (52)Mn recovery. In vitro uptake of Mn-based PET and MRI contrast agents ((52)Mn(2+) and Mn(2+), 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.
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lewis
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Graves
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Hector F
authors.initials: HF
authors.lastname: Valdovinos
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.affiliation: 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;
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA; ; 2. Department of Radiology, University of Wisconsin - Madison, Madison, WI, USA; ; 4. Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Mary E
authors.initials: ME
authors.lastname: Meyerand
authors.affiliation: 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.affiliation: 5. Department of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000302:isolation & purification; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000302:isolation & purification; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry*; D014157:Transcription Factors / Q000032:analysis*
chemical_list: C110547:DMRT1 protein; D011868:Radioisotopes; D014157:Transcription Factors; D008345:Manganese
keywords: Positron emission tomography (PET); cell tracking; manganese-52 (52Mn); manganese-enhanced magnetic resonance imaging (MEMRI); multimodality imaging; reporter gene.