Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography

Terrovitis, John; Kwok, Keng Fai; Lautamäki, Riikka; Engles, James; Barth, Andreas S.; Kizana, Eddy; Miake, Junichiro; Leppo, Michelle K.; Fox, James J.; Seidel, Jürgen; Pomper, Martin G.; Wahl, Richard L.; Tsui, B.M.W.; Bengel, Frank M.; Marbán, Eduardo; Abraham, M. Roselle

doi:10.1016/j.jacc.2008.06.051

Cited by 158 publications

(153 citation statements)

References 27 publications

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“…NIS overexpression was also reported for several nonthyroidal cancer types including colorectal, lung, and a subset of breast cancers (13,(20)(21)(22)(23)(24), but it remains to be determined if those NIS expression levels are sufficient and consistent enough for accurate diagnosis and therapy. NIS has also been used as a reporter gene preclinically in cardiac (25), hematopoietic (26), and neural studies (27); for tracking macrophage migration (28); and for noninvasive imaging of gene therapy vectors (29,30). It has not yet been used for cancer metastasis tracking.…”

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confidence: 99%

A Whole-Body Dual-Modality Radionuclide Optical Strategy for Preclinical Imaging of Metastasis and Heterogeneous Treatment Response in Different Microenvironments

et al. 2014

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Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in vivo is difficult to achieve. The goal was to develop a new highly sensitive and reliable preclinical longitudinal in vivo imaging model for this purpose, thereby facilitating discovery and validation of anticancer therapies or molecular imaging agents. Methods: The strategy is based on breast cancer cells stably expressing the human sodium iodide symporter (NIS) fused to a red fluorescent protein, thereby permitting radionuclide and fluorescence imaging. Using whole-body nano-SPECT/CT with 99m TcO 4 − , we followed primary tumor growth and spontaneous metastasis in the presence or absence of etoposide treatment. NIS imaging was used to classify organs as small as individual lymph nodes (LNs) to be positive or negative for metastasis, and results were confirmed by confocal fluorescence microscopy. Etoposide treatment efficacy was proven by ex vivo anticaspase 3 staining and fluorescence microscopy. Results: In this preclinical model, we found that the NIS imaging strategy outperformed stateof-the-art 18 F-FDG imaging in its ability to detect small tumors (18.5-fold-better tumor-to-blood ratio) and metastases (LN, 3.6-fold) because of improved contrast in organs close to metastatic sites (12-and 8.5-fold-lower standardized uptake value in the heart and kidney, respectively). We applied the model to assess the treatment response to the neoadjuvant etoposide and found a consistent and reliable improvement in spontaneous metastasis detection. Importantly, we also found that tumor cells in different microenvironments responded in a heterogeneous manner to etoposide treatment, which could be determined only by the NIS-based strategy and not by 18 F-FDG imaging. Conclusion: We developed a new strategy for preclinical longitudinal in vivo cancer cell tracking with greater sensitivity and reliability than 18 F-FDG PET and applied it to track spontaneous and distant metastasis in the presence or absence of genotoxic stress therapy. Importantly, the model provides sufficient sensitivity and dynamic range to permit the reliable assessment of heterogeneous treatment responses in various microenvironments.

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confidence: 99%

A Whole-Body Dual-Modality Radionuclide Optical Strategy for Preclinical Imaging of Metastasis and Heterogeneous Treatment Response in Different Microenvironments

et al. 2014

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“…NIS genes can be used as imaging reporter genes in PET as well as SPECT imaging, because they concentrate radionuclides such as 124 I, 131 I, and 99m Tc-pertechnetate, which can be visualized by conventional γ-camera or PET [64][65][66]. Terrovitis et al showed that NIS-expressing (NIS + ) rat cardiac-derived stem cells (rCDCs) were visualized in vivo up to 6 days post-injection in a rat MI model by SPECT [67]. Lee et al showed that intramyocardially injected rats with NIS-expressing adenovirus-transfected canine stem cells (Ad-hNIS-canine ADSCs) were monitored for 9 days in the canine MI model by 99m Tc-pertechnetate ( 99m TcO4 − ) SPECT imaging (Fig.…”

Section: Indirect Labelingmentioning

confidence: 99%

Stem Cell Monitoring with a Direct or Indirect Labeling Method

Kim

Lee

Kang

2015

Nucl Med Mol Imaging

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The molecular imaging techniques allow monitoring of the transplanted cells in the same individuals over time, from early localization to the survival, migration, and differentiation. Generally, there are two methods of stem cell labeling: direct and indirect labeling methods. The direct labeling method introduces a labeling agent into the cell, which is stably incorporated or attached to the cells prior to transplantation. Direct labeling of cells with radionuclides is a simple method with relatively fewer adverse events related to genetic responses. However, it can only allow short-term distribution of transplanted cells because of the decreasing imaging signal with radiodecay, according to the physical half-lives, or the signal becomes more diffuse with cell division and dispersion. The indirect labeling method is based on the expression of a reporter gene transduced into the cell before transplantation, which is then visualized upon the injection of an appropriate probe or substrate. In this review, various imaging strategies to monitor the survival and behavior change of transplanted stem cells are covered. Taking these new approaches together, the direct and indirect labeling methods may provide new insights on the roles of in vivo stem cell monitoring, from bench to bedside.

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“…The final obstacle is the inadequate conditions for engraftment since there is no pre-established vasculature present to nourish the transplanted cells (Martens, et al, 2009). In some cases, there will be little or no space for the cells to divide into since the target tissue has no cavity (Darabi, et al, 2009;Laflamme, et al, 2007;Terrovitis, et al, 2008). It is no surprise that most transplanted cells die within 24 hours of transplantation (Bliss, et al, 2007;Guerette, et al, 1997;Snyder, et al, 2010;Suzuki, et al, 2004;Tate, et al, 2009;Terrovitis, et al, 2008;Zhong, et al, 2010 (Kaihara and Vacanti, 1999).…”

Section: Challenges For Novel Stem Cell-based Therapiesmentioning

confidence: 99%

“…In short, the transplanted stem cells need help to stay alive long enough for their therapeutic effect to be seen. The majority of stem and progenitor cells in the transplanted bolus die shortly after transplantation (Bliss, et al, 2007;Snyder, et al, 2010;Terrovitis, et al, 2008;Zhong, et al, 2010). In some cases, more than 95% of transplanted stem cells die within two weeks of transplantation (Snyder, et al, 2010;Terrovitis, et al, 2008;Zhong, et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…The majority of stem and progenitor cells in the transplanted bolus die shortly after transplantation (Bliss, et al, 2007;Snyder, et al, 2010;Terrovitis, et al, 2008;Zhong, et al, 2010). In some cases, more than 95% of transplanted stem cells die within two weeks of transplantation (Snyder, et al, 2010;Terrovitis, et al, 2008;Zhong, et al, 2010). Since tissues contain cells encapsulated in a carbohydrate and protein-rich extracellular matrix (ECM), one approach to significantly improve stem cell survival is to include a biomaterial carrier that acts as an ECM mimic upon in vivo delivery.…”

Section: Introductionmentioning

confidence: 99%

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The Use of a Hydrogel Matrix as a Cellular Delivery Vehicle in Future Cell-Based Therapies: Biological and Non-Biological Considerations

Zarembinski¹,

Tew²,

Atzet³

2011

Regenerative Medicine and Tissue Engineering - Cells and Biomaterials

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Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography

Cited by 158 publications

References 27 publications

A Whole-Body Dual-Modality Radionuclide Optical Strategy for Preclinical Imaging of Metastasis and Heterogeneous Treatment Response in Different Microenvironments

A Whole-Body Dual-Modality Radionuclide Optical Strategy for Preclinical Imaging of Metastasis and Heterogeneous Treatment Response in Different Microenvironments

Stem Cell Monitoring with a Direct or Indirect Labeling Method

The Use of a Hydrogel Matrix as a Cellular Delivery Vehicle in Future Cell-Based Therapies: Biological and Non-Biological Considerations

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