In vivo imaging of ligand receptor binding with Gaussia luciferase complementation

Luker, Gary D.; Mihalko, Laura Anne; Schmidt, Bradley T.; Lewin, Sarah A.; Ray, Paramita; Shcherbo, Dmitry; Chudakov, Dmitriy M.

doi:10.1038/nm.2590

Cited by 66 publications

(75 citation statements)

References 27 publications

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“…Breast cancer cells can express both of the CXCL12/SDF-1 receptors, CXCR4 and the alternative inhibitory receptor CXCR7 (48). To confirm POL5551’s specificity for CXCR4 over CXCR7, we utilized a complementation-imaging model (35), in which the N terminal portion of the Gaussia luciferase (GLuc) is fused to CXCR4 or CXCR7 while the C terminal portion of GLuc is fused to the ligand SDF-1. In the presence of coelenterazine, reconstitution of GLuc and subsequent light production serves as a quantitative measure of receptor-ligand binding and POL5551 bioactivity (Supplemental Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

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CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer

Xiang

Hurchla

Fontana³

et al. 2015

Molecular Cancer Therapeutics

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The SDF-1-receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow disseminated tumor cells (DTC) negative patients at high risk for metastasis and death. The Protein Epitope Mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared to single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we utilized a “chemotherapy framing” dosing strategy. When administered shortly before and after eribulin treatment, 3 doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases.

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Section: Resultsmentioning

confidence: 99%

“…CXCL12-CGLuc, NGLuc-CXCR4, and NGLuc-CXCR7 MDA-MB-231 cells were generated as previously described (35). …”

Section: Methodsmentioning

confidence: 99%

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer

Xiang

Hurchla

Fontana³

et al. 2015

Molecular Cancer Therapeutics

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“…As the physical phantom was turned and imaged, it was shown that the maximum intensity in images decreased dramatically as a function of angle, and it is seen that there is a 10-fold drop in total top-view intensity in images over the range in which the majority of the flux was physically visible (sets 1 to 5). This is a dramatic change given that this method is presently used for quantification in biomedical studies [1,3,30] and the actual surface flux was the same in each case. Applying backprojection did not improve results, but when applying the proposed method the reconstructed flux was stable as a function of angle.…”

Section: Discussionmentioning

confidence: 99%

Quantitative surface radiance mapping using multiview images of light-emitting turbid media

et al. 2013

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A novel method is presented for accurately reconstructing a spatially resolved map of diffuse light flux on a surface using images of the surface and a model of the imaging system. This is achieved by applying a model-based reconstruction algorithm with an existing forward model of light propagation through free space that accounts for the effects of perspective, focus, and imaging geometry. It is shown that flux can be mapped reliably and quantitatively accurately with very low error, <3% with modest signal-to-noise ratio. Simulation shows that the method is generalizable to the case in which mirrors are used in the system and therefore multiple views can be combined in reconstruction. Validation experiments show that physical diffuse phantom surface fluxes can also be reconstructed accurately with variability <3% for a range of object positions, variable states of focus, and different orientations. The method provides a new way of making quantitatively accurate noncontact measurements of the amount of light leaving a diffusive medium, such as a small animal containing fluorescent or bioluminescent markers, that is independent of the imaging system configuration and surface position.

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“…Specifically, they quantified the binding of chemokine (C-X-C motif) ligand 12 (CXCL12) to chemokine (C-X-C motif) receptors 4 (CXCR4) and 7 (CXCR7). BLI showed CXCL12-CXCR7 binding in primary and metastatic tumors in a mouse model of breast cancer and enabled them to quantify the drug-mediated inhibition of CXCL12-CXCR4 binding in living mice [79]. …”

Section: Reporter Genes For Bioluminescence Imagingmentioning

confidence: 99%

New imaging probes to track cell fate: reporter genes in stem cell research

Jurgielewicz

Harmsen

Wei

et al. 2017

Cell. Mol. Life Sci.

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Cell fate is a concept used to describe the differentiation and development of a cell in its organismal context over time. It is important in the field of regenerative medicine, where stem cell therapy holds much promise but is limited by our ability to assess its efficacy, which is mainly due to the inability to monitor what happens to the cells upon engraftment to the damaged tissue. Currently, several imaging modalities can be used to track cells in the clinical setting; however, they do not satisfy many of the criteria necessary to accurately assess several aspects of cell fate. In recent years, reporter genes have become a popular option for tracking transplanted cells, via various imaging modalities in small mammalian animal models. This review article examines the reporter gene strategies used in imaging modalities such as MRI, SPECT/PET, Optoacoustic and Bioluminescence Imaging. Strengths and limitations of the use of reporter genes in each modality are discussed.

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In vivo imaging of ligand receptor binding with Gaussia luciferase complementation

Cited by 66 publications

References 27 publications

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer

Quantitative surface radiance mapping using multiview images of light-emitting turbid media

New imaging probes to track cell fate: reporter genes in stem cell research

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