Negrin, R.S. & Contag, C.H. In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease. Nat. Rev. Immunol. 6, 484-490

Department of Medicine, Center for Clinical Research Building, 269 West Campus Drive, Stanford University, Stanford, California 94305, USA.
Nature reviews. Immunology (Impact Factor: 34.99). 07/2006; 6(6):484-90. DOI: 10.1038/nri1879
Source: PubMed


Immunological reactions have a key role in health and disease and are complex events characterized by coordinated cell trafficking to specific locations throughout the body. Clarification of these cell-trafficking events is crucial for improving our understanding of how immune reactions are initiated, controlled and recalled. As we discuss here, an emerging modality for revealing cell trafficking is bioluminescence imaging, which harnesses the light-emitting properties of enzymes such as luciferase for quantification of cells and uses low-light imaging systems. This strategy could be useful for the study of a wide range of biological processes, such as the pathophysiology of graft-versus-host and graft-versus-leukaemia reactions.

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Available from: Christopher H Contag
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    • "Bioluminescence reporter proteins have been widely used in the development of tools for monitoring biological events in living organisms in real time [21]. Many aspects of drug development can be facilitated using bioluminescence reporter proteins as an indicator to discover new targets, identify novel drug candidates, and validate their potency [22], [23]. In the present study, we found that a reporter consisting of cyclin A2 fused to luciferase was responsive to S-phase-specific anti-cancer drug, HCPT in cellulo and in vivo. "
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    ABSTRACT: Bioluminescence reporter proteins have been widely used in the development of tools for monitoring biological events in living cells. Currently, some assays like flow cytometry analysis are available for studying DNA synthetic phase (S-phase) targeted anti-cancer drug activity in vitro; however, techniques for imaging of in vivo models remain limited. Cyclin A2 is known to promote S-phase entry in mammals. Its expression levels are low during G1-phase, but they increase at the onset of S-phase. Cyclin A2 is degraded during prometaphase by ubiquitin-dependent, proteasome-mediated proteolysis. In this study, we have developed a cyclin A2-luciferase (CYCA-Luc) fusion protein targeted for ubiquitin-proteasome dependent degradation, and have evaluated its utility in screening S-phase targeted anti-cancer drugs. Similar to endogenous cyclin A2, CYCA-Luc accumulates during S-phase and is degraded during G2/M-phase. Using Cdc20 siRNA we have demonstrated that Cdc20 can mediate CYCA-Luc degradation. Moreover, using noninvasive bioluminescent imaging, we demonstrated accumulation of CYCA-Luc in response to 10-hydroxycamptothecin (HCPT), an S-phase targeted anti-cancer drug, in human tumor cells in vivo and in vitro. Our results indicate that a CYCA-Luc fusion reporter system can be used to monitor S-phase of cell cycle, and evaluate pharmacological activity of anti-cancer drug HCPT in real time in vitro and in vivo, and is likely to provide an important tool for screening such drugs.
    Full-text · Article · Jan 2013 · PLoS ONE
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    • "Bioluminescence imaging exploits the emission of visible photons at specific wavelengths based on energy-dependent reactions catalyzed by luciferases 66. These reactions require a substrate, and for insect luciferases also require ATP, magnesium and oxygen. "
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    ABSTRACT: Biological cancer therapies, such as oncolytic, or replication-selective viruses have advantages over traditional therapeutics as they can employ multiple different mechanisms to target and destroy cancers (including direct cell lysis, immune activation and vascular collapse). This has led to their rapid recent clinical development. However this also makes their pre-clinical and clinical study complex, as many parameters may affect their therapeutic potential and so defining reason for treatment failure or approaches that might enhance their therapeutic activity can be complicated. The ability to non-invasively image viral gene expression in vivo both in pre-clinical models and during clinical testing will considerably enhance the speed of oncolytic virus development as well as increasing the level and type of useful data produced from these studies. Further, subsequent to future clinical approval, imaging of reporter gene expression might be used to evaluate the likelihood of response to oncolytic viral therapy prior to changes in tumor burden. Here different reporter genes used in conjunction with oncolytic viral therapy are described, along with the imaging modalities used to measure their expression, while their applications both in pre-clinical and clinical testing are discussed. Possible future applications for reporter gene expression from oncolytic viruses in the phenotyping of tumors and the personalizing of treatment regimens are also discussed.
    Preview · Article · Apr 2012 · Theranostics
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    • "Bioluminescence tomography (BLT) is a rapidly growing field of research in optical molecular imaging, which allows for the visualization of normal and abnormal cellular processes in living subjects at the molecular or genetic level [1–4]. With BLT, we seek to recover the spatial distribution of bioluminescent light source inside a small animal from external noninvasive measurements [5]. "
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    ABSTRACT: A finite element mesh aggregating approach is presented to reconstruct images of multiple internal bioluminescence sources. Rather than assuming independence between mesh nodes, the proposed reconstruction strategy exploits spatial structure of nodes and aggregation feature of density distribution on the finite element mesh to adaptively determine the number of sources and to improve the quality of reconstructed images. With the proposed strategy integrated in the regularization-based reconstruction process, reconstruction algorithms need no a priori knowledge of source number; even more importantly, they can automatically reconstruct multiple sources that differ greatly in density or power.
    Full-text · Article · Nov 2011 · International Journal of Biomedical Imaging
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