MRI Reporter Genes

Gilad, Assaf A.; Ziv, Keren; McMahon, Michael T.; Zijl, Peter van; Neeman, Michal; Bulte, Jeff W.M.

doi:10.2967/jnumed.108.053520

Cited by 110 publications

(80 citation statements)

References 27 publications

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“…MR imaging reporter gene methods are well suited for this purpose and are emerging alternatives to conventional cell-labeling strategies (12,13). A prominent MR imaging reporter gene method uses cellular overexpression of proteins responsible for maintaining iron homeostasis, notably ferritin, to generate R2 and/or R2* contrast on images of reporter gene-expressing cells (14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Cell Preparationmentioning

confidence: 99%

Ovarian Carcinoma: Quantitative Biexponential MR Imaging Relaxometry Reveals the Dynamic Recruitment of Ferritin-expressing Fibroblasts to the Angiogenic Rim of Tumors

Vandsburger

Radoul²,

Addadi³

et al. 2013

Radiology

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Purpose:To quantitatively monitor the dynamic perivascular recruitment of ferritin heavy chain (FHC)-overexpressing fibroblasts to ovarian carcinoma xenografts by using R2 mapping and biexponential magnetic resonance (MR) relaxometry. Materials andMethods:In vivo studies of female mice were approved by the institutional animal care and use committee. In vitro analysis included MR-based R2 relaxation measurements of monkey kidney cell line (CV1) fibroblasts that overexpress FHC, followed by inductively coupled plasma mass spectrometry to assess cellular iron content. For in vivo analysis, CV1-FHC fibroblasts were either mixed with fluorescent human ovarian carcinoma cells before subcutaneous implantation (coinjection) or injected intraperitoneally 4 days after the cancer cells were injected (remote recruitment). Dynamic changes in tumor R2 were used to derive CV1-FHC cell fraction in both models. In coinjection tumors, dynamic contrast material-enhanced MR imaging was used to measure tumor fractional blood volume. Whole-body fluorescence imaging and immunohistochemical staining were performed to validate MR results. One-way repeated measures analysis of variance was used to assess MR and fluorescence imaging results and tumor volume, and one-way analysis of variance was used to assess spectrometric results, fractional blood volume, and immunohistochemical evaluation. Results:CV1-FHC fibroblasts (vs CV1 fibroblasts) showed enhanced iron uptake (1.8 mmol 6 0.5 3 10 28 vs 0.9 mmol 6 0.5 3 10 28 ; P , .05), retention (1.6 mmol 6 0.5 3 10 28 vs 0.5 mmol 6 0.5 3 10 28 , P , .05), and cell density-dependent R2 contrast. R2 mapping in vivo revealed preferential recruitment of CV1-FHC cells to the tumor rim in both models. Measurement of fractional blood volume was similar in all tumors (2.6 AU 6 0.5 3 10 23 for CV1, 2.3 AU 6 0.3 3 10 23 for CV1-FHC, 2.9 6 0.3 3 10 23 for CV1-FHC-ferric citrate). Dynamic changes in CV1-FHC cell fraction determined at MR relaxometry in both models were confirmed at immunohistochemical analysis. Conclusion:FHC overexpression, when combined with R2 mapping and MR relaxometry, enabled in vivo detection of the dynamic recruitment of exogenously administered fibroblasts to the vasculature of solid tumors.

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Section: Cell Preparationmentioning

confidence: 99%

Ovarian Carcinoma: Quantitative Biexponential MR Imaging Relaxometry Reveals the Dynamic Recruitment of Ferritin-expressing Fibroblasts to the Angiogenic Rim of Tumors

Vandsburger

Radoul²,

Addadi³

et al. 2013

Radiology

Self Cite

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“…87 MRI-based approaches rely on factors including: (1) enzyme-based reporter genes including β-galactosidase, which cleaves galactose form specific contrast agents; (2) expressions of surface receptors that enable binding of specific MR contrast agents; and (3) expressions of endogenous irons, such as tyrosinase, transferrin receptor, and ferritin. 88,89 Bengtsson et al 90 used lacZ as an MRI reporter gene for in vitro and in vivo MR imaging of mouse BMSCs. Chung et al 91 also reported the combination of myc and hemagglutinin A antigen-expressing reporter gene and SPIO-conjugated antibody techniques for detecting early mouse ESC-derived teratoma formation in injured mouse myocardium.…”

Section: Current Stem Cell Imaging Technologiesmentioning

confidence: 99%

Molecular imaging for In vivo tracking of stem cell fate

et al. 2014

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Stem cells have a potential to dramatically change the common modalities of treatment for many diseases. Despite their rapid transition from animal studies to clinical applications, a number of unanswered questions remain regarding in vivo behaviors of stem cells transplanted into target tissues, including questions about their survival, distribution, migration, differentiation, and tumorigenicity. Recent advances in noninvasive molecular imaging technologies, including optical imaging, magnetic resonance imaging (MRI), radionuclide imaging, and reporter genebased imaging, have gradually elucidated the fundamental behaviors of stem cells via in vivo real time qualitative and quantitative monitoring. Here, we briefly review current imaging techniques for tracking stem cells, with an emphasis on the advantages and drawbacks of each imaging approach, and discuss future prospects for in vivo tracking of stem cells in regenerative medicine.

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“…Bulte and colleagues classiˆed 3 categories of MR imaging reporters-enzymebased, chemical exchange saturation transfer (CEST)-based, and iron-based. 35 b-Galactosidase, encoded by the bacterial gene lacZ, is suggested as an enzyme-based MR imaging reporter gene and has long been used to assess gene transfer and its expression in vivo as well as in vitro with colored substrates. 36 Taking advantage of its well established chemical reactions, gadoliniumbased MR imaging contrast agents were designed that function as substrates for b-Galactosidase.…”

Section: Mr Imaging Reporter Genesmentioning

confidence: 99%

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

2010

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Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic e‹cacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene.

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MRI Reporter Genes

Cited by 110 publications

References 27 publications

Ovarian Carcinoma: Quantitative Biexponential MR Imaging Relaxometry Reveals the Dynamic Recruitment of Ferritin-expressing Fibroblasts to the Angiogenic Rim of Tumors

Ovarian Carcinoma: Quantitative Biexponential MR Imaging Relaxometry Reveals the Dynamic Recruitment of Ferritin-expressing Fibroblasts to the Angiogenic Rim of Tumors

Molecular imaging for In vivo tracking of stem cell fate

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

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