⁵²Mn production for PET/MRI tracking of human stem cells expressing divalent metal transporter 1 (DMT1).

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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.

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Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state.

Sean Deoni, Brian Rutt, Terry M Peters (2003)

A novel, fully 3D, high-resolution T(1) and T(2) relaxation time mapping method is presented. The method is based on steady-state imaging with T(1) and T(2) information derived from either spoiling or fully refocusing the transverse magnetization following each excitation pulse. T(1) is extracted from a pair of spoiled gradient recalled echo (SPGR) images acquired at optimized flip angles. This T(1) information is combined with two refocused steady-state free precession (SSFP) images to determine T(2). T(1) and T(2) accuracy was evaluated against inversion recovery (IR) and spin-echo (SE) results, respectively. Error within the T(1) and T(2) maps, determined from both phantom and in vivo measurements, is approximately 7% for T(1) between 300 and 2000 ms and 7% for T(2) between 30 and 150 ms. The efficiency of the method, defined as the signal-to-noise ratio (SNR) of the final map per voxel volume per square root scan time, was evaluated against alternative mapping methods. With an efficiency of three times that of multipoint IR and three times that of multiecho SE, our combined approach represents the most efficient of those examined. Acquisition time for a whole brain T(1) map (25 x 25 x 10 cm) is less than 8 min with 1 mm(3) isotropic voxels. An additional 7 min is required for an identically sized T(2) map and postprocessing time is less than 1 min on a 1 GHz PIII PC. The method therefore permits real-time clinical acquisition and display of whole brain T(1) and T(2) maps for the first time. Copyright 2003 Wiley-Liss, Inc.

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Superparamagnetic Iron Oxide Nanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking

Li Li, Hao-wen Jiang, Kui Luo … (2013)

Stem cells hold great promise for the treatment of multiple human diseases and disorders. Tracking and monitoring of stem cells in vivo after transplantation can supply important information for determining the efficacy of stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be the most effective and safest non-invasive technique for stem cell tracking in living bodies. Commercial superparamagnetic iron oxide nanoparticles (SPIONs) in the aid of transfection agents (TAs) have been applied to labeling stem cells. However, owing to the potential toxicity of TAs, more attentions have been paid to develop novel SPIONs with specific surface coating or functional moieties which facilitate effective cell internalization in the absence of TAs. This review aims to summarize the recent progress in the design and preparation of SPIONs as cellular MRI probes, to discuss their applications and current problems facing in stem cell labeling and tracking, and to offer perspectives and solutions for the future development of SPIONs in this field.

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A new method for the rapid and long term growth of human neural precursor cells.

Clive Svendsen, Melanie G ter Borg, Richard J.E Armstrong … (1998)

A reliable source of human neural tissue would be of immense practical value to both neuroscientists and clinical neural transplantation trials. In this study, human precursor cells were isolated from the developing human cortex and, in the presence of both epidermal and fibroblast growth factor-2, grew in culture as sphere shaped clusters. Using traditional passaging techniques and culture mediums the rate of growth was extremely slow, and only a 12-fold expansion in total cell number could be achieved. However, when intact spheres were sectioned into quarters, rather than mechanically dissociated, cell cell contacts were maintained and cellular trauma minimised which permitted the rapid and continual growth of each individual quarter. Using this method we have achieved a 1.5 million-fold increase in precursor cell number over a period of less than 200 days. Upon differentiation by exposure to a substrate, cells migrated out from the spheres and formed a monolayer of astrocytes and neurons. No oligodendrocytes were found to develop from these human neural precursor cells at late passages when whole spheres were differentiated. This simple and novel culture method allows the rapid expansion of large numbers of non-transformed human neural precursor cells which may be of use in drug discovery, ex vivo gene therapy and clinical neural transplantation.

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Author and article information

Journal

Journal ID (iso-abbrev): Theranostics

Title: Theranostics

Publisher: Ivyspring International Publisher

ISSN (Electronic): 1838-7640

ISSN (Print): 1838-7640

Publication date (Electronic): 2015

Volume: 5

Issue: 3

Affiliations

[1 ] 1. Department of Medical Physics, University of Wisconsin - Madison, Madison, WI, USA;

[2 ] 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;

[3 ] 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;

[4 ] 5. Department of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA.

Article

Publisher Item ID: thnov05p0227

DOI: 10.7150/thno.10185

PMC ID: 4279187

PubMed ID: 25553111

SO-VID: 6835ae32-4396-49e3-87c1-ff25efcfb1e3

History

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

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

⁵²Mn production for PET/MRI tracking of human stem cells expressing divalent metal transporter 1 (DMT1).

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Most cited references 32

Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state.

Superparamagnetic Iron Oxide Nanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking

A new method for the rapid and long term growth of human neural precursor cells.

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