It's not just about anatomy: In vivo bioluminescence imaging as an eyepiece into biology

Among the newly described tools that enable analyses of cellular and molecular events in living animals, in vivo bioluminescence imaging (BLI) offers important opportunities for investigating a wide variety of disease processes. BLI utilizes luciferase as an internal biological light source that can be genetically programmed to noninvasively “report” the presence or activation of specific biological events. Applications of BLI have included the use of luciferase to demonstrate expression of cell‐ and tissue‐specific promoters, label cell populations, guide detection by other imaging modalities, and detect protein‐protein interaction. These applications of BLI technology have allowed quantitative measurements of tumor burden and treatment response, immune cell trafficking, and detection of gene transfer. Spatiotemporal information can be rapidly obtained in the context of whole biological systems in vivo, which can accelerate the development of experimental therapeutic strategies. This paper provides a review of the biological applications in which in vivo BLI has been utilized to nondestructively monitor biological processes in intact small animal models, and highlights some of the advancements that will increase the versatility of BLI as a molecular imaging tool. J. Magn. Reson. Imaging 2002;16:378–387. © 2002 Wiley‐Liss, Inc.

[1]  C E Hooper,et al.  CCD imaging of luciferase gene expression in single mammalian cells. , 1990, Journal of bioluminescence and chemiluminescence.

[2]  A. Welch,et al.  A review of the optical properties of biological tissues , 1990 .

[3]  N Kajiyama,et al.  Isolation and characterization of mutants of firefly luciferase which produce different colors of light. , 1991, Protein engineering.

[4]  S. Kay,et al.  A novel circadian phenotype based on firefly luciferase expression in transgenic plants. , 1992, The Plant cell.

[5]  S. Pietrokovski,et al.  Conserved sequence features of inteins (protein introns) and their use in identifying new inteins and related proteins , 1994, Protein science : a publication of the Protein Society.

[6]  E. Davis,et al.  The ins and outs of protein splicing elements , 1994, Molecular microbiology.

[7]  R. Weinberg,et al.  Tumor spectrum analysis in p53-mutant mice , 1994, Current Biology.

[8]  C E Hooper,et al.  Low-light imaging technology in the life sciences. , 1994, Journal of bioluminescence and chemiluminescence.

[9]  Neil D. Clarke.  A proposed mechanism for the self-splicing of proteins. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Nicholson,et al.  Real time measurement of gene expression in living endocrine cells. , 1994, Endocrinology.

[11]  J. Mullins,et al.  Photonic detection of bacterial pathogens in living hosts , 1995, Molecular microbiology.

[12]  C. Strayer,et al.  Circadian clock mutants in Arabidopsis identified by luciferase imaging , 1995, Science.

[13]  J. Renard,et al.  Real time imaging of transcriptional activity in live mouse preimplantation embryos using a secreted luciferase. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Braddock,et al.  Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells. , 1995, Journal of cell science.

[15]  J. W. Hastings,et al.  Chemistries and colors of bioluminescent reactions: a review. , 1996, Gene.

[16]  P. Brick,et al.  Crystal structure of firefly luciferase throws light on a superfamily of adenylate-forming enzymes. , 1996, Structure.

[17]  T. Baldwin,et al.  Firefly luciferase: the structure is known, but the mystery remains. , 1996, Structure.

[18]  Andrew J. Millar,et al.  Real-time imaging of transcription in living cells and tissues. , 1996, Biochemical Society transactions.

[19]  Y. Miyagi,et al.  Governing step of metastasis visualized in vitro. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[20]  D A Benaron,et al.  Tissue Optics , 1997, Science.

[21]  David K. Stevenson,et al.  Tissue Optics , 1997, Science.

[22]  Simon R. Cherry,et al.  An evaluation of exact and approximate 3-D reconstruction algorithms for a high-resolution, small-animal PET scanner , 1998, IEEE Transactions on Medical Imaging.

[23]  R. Day,et al.  Dual-function reporter protein for analysis of gene expression in living cells. , 1998, BioTechniques.

[24]  S. Cherry,et al.  Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  J. Humm,et al.  Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. , 1998, Cancer research.

[26]  T P Sandalova,et al.  Model of the active site of firefly luciferase. , 1999, Biochemistry. Biokhimiia.

[27]  A. Jacobs,et al.  Functional coexpression of HSV-1 thymidine kinase and green fluorescent protein: implications for noninvasive imaging of transgene expression. , 1999, Neoplasia.

[28]  C. Contag,et al.  Noninvasive assessment of tumor cell proliferation in animal models. , 1999, Neoplasia.

[29]  S. Anderson,et al.  Site-directed mutagenesis of firefly luciferase active site amino acids: a proposed model for bioluminescence color. , 1999, Biochemistry.

[30]  S. Cherry,et al.  Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[31]  R G Blasberg,et al.  Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Sandalova Tp,et al.  Model of the active site of firefly luciferase. , 1999 .

[33]  R. Jain,et al.  Changes in vascularization of human breast cancer xenografts responding to antiestrogen therapy. , 1999, Neoplasia.

[34]  C. Contag,et al.  Visualizing the kinetics of tumor-cell clearance in living animals. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Jacks,et al.  Insights into cancer from transgenic mouse models , 1999, The Journal of pathology.

[36]  S. Larson,et al.  A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase. , 1999, Neoplasia.

[37]  J. M. Taylor,et al.  Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. , 2000, Journal of the National Cancer Institute.

[38]  Imaging in cancer: a National Cancer Institute "extraordinary opportunity". , 2000, Neoplasia.

[39]  J. Fujimoto,et al.  Optical coherence tomography: an emerging technology for biomedical imaging and optical biopsy. , 2000, Neoplasia.

[40]  D. Mankoff,et al.  Characterizing tumors using metabolic imaging: PET imaging of cellular proliferation and steroid receptors. , 2000, Neoplasia.

[41]  R. Gillies,et al.  Applications of magnetic resonance in model systems: cancer therapeutics. , 2000, Neoplasia.

[42]  M J Paulus,et al.  High resolution X-ray computed tomography: an emerging tool for small animal cancer research. , 2000, Neoplasia.

[43]  J. Trempe,et al.  Luminometric quantitation of photinus pyralis firefly luciferase and Escherichia coli beta-galactosidase in blood-contaminated organ lysates. , 2000, Analytical biochemistry.

[44]  J Kurhanewicz,et al.  Three-dimensional magnetic resonance spectroscopic imaging of brain and prostate cancer. , 2000, Neoplasia.

[45]  C. Contag,et al.  Use of reporter genes for optical measurements of neoplastic disease in vivo. , 2000, Neoplasia.

[46]  R. Gillies,et al.  Applications of magnetic resonance in model systems: tumor biology and physiology. , 2000, Neoplasia.

[47]  R Weissleder,et al.  Improvement of MRI probes to allow efficient detection of gene expression. , 2000, Bioconjugate chemistry.

[48]  Bonnie F. Sloane,et al.  Imaging proteolysis by living human breast cancer cells. , 2000, Neoplasia.

[49]  S. Larson,et al.  Imaging transgene expression with radionuclide imaging technologies. , 2000, Neoplasia.

[50]  J. Capeau,et al.  Haemoglobin interferes with the ex vivo luciferase luminescence assay: consequence for detection of luciferase reporter gene expression in vivo , 2000, Gene Therapy.

[51]  Y. Wang,et al.  Visualizing and quantifying protein secretion using a Renilla luciferase-GFP fusion protein. , 2000, Luminescence : the journal of biological and chemical luminescence.

[52]  N. Ramanujam.  Fluorescence spectroscopy of neoplastic and non-neoplastic tissues. , 2000, Neoplasia.

[53]  T L Chenevert,et al.  Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[54]  L. Svaasand,et al.  Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy. , 2000, Neoplasia.

[55]  R. Gillies,et al.  Imaging prostate cancer invasion with multi-nuclear magnetic resonance methods: the Metabolic Boyden Chamber. , 2000, Neoplasia.

[56]  Daniel E. Hall,et al.  Rapid and quantitative assessment of cancer treatment response using in vivo bioluminescence imaging. , 2000, Neoplasia.

[57]  Daniel J. Hawrysz,et al.  Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. , 2000, Neoplasia.

[58]  A. Ullrich,et al.  Intravital fluorescence videomicroscopy to study tumor angiogenesis and microcirculation. , 2000, Neoplasia.

[59]  H. Shimada,et al.  Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[60]  G. Navon,et al.  HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary cancer cells. , 2000, Neoplasia.

[61]  A. Szalay,et al.  Detection of GDNF secretion in glial cell culture and from transformed cell implants in the brains of live animals , 2001, Molecular Genetics and Genomics.

[62]  D. Vordermark,et al.  Green fluorescent protein is a suitable reporter of tumor hypoxia despite an oxygen requirement for chromophore formation. , 2001, Neoplasia.

[63]  P. Kristjansen,et al.  Quantitative estimates of vascularity in solid tumors by non-invasive near-infrared spectroscopy. , 2001, Neoplasia.

[64]  J. Humm,et al.  Using positron emission tomography with [(18)F]FDG to predict tumor behavior in experimental colorectal cancer. , 2001, Neoplasia.

[65]  C. Contag,et al.  Bioluminescence imaging of lymphocyte trafficking in vivo. , 2001, Experimental hematology.

[66]  M. Iyer,et al.  Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[67]  S. Gambhir,et al.  Optical imaging of Renilla luciferase reporter gene expression in living mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  C. Contag,et al.  Adoptive Immunotherapy of Experimental Autoimmune Encephalomyelitis Via T Cell Delivery of the IL-12 p40 Subunit1 , 2001, The Journal of Immunology.

[69]  E. Galun,et al.  Imaging transgene expression in live animals. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[70]  S S Gambhir,et al.  Noninvasive optical imaging of firefly luciferase reporter gene expression in skeletal muscles of living mice. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[71]  C. Contag,et al.  Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis. , 2001, The Journal of clinical investigation.

[72]  C Zimmer,et al.  Magnetic labeling of activated microglia in experimental gliomas. , 2001, Neoplasia.

[73]  D Artemov,et al.  Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. , 2001, Neoplasia.

[74]  B. Rice,et al.  In vivo imaging of light-emitting probes. , 2001, Journal of biomedical optics.

[75]  P. Kristjansen,et al.  Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro. , 2001, Neoplasia.

[76]  Y. Umezawa,et al.  Split luciferase as an optical probe for detecting protein-protein interactions in mammalian cells based on protein splicing. , 2001, Analytical chemistry.

[77]  Y. Wang,et al.  A study of protein-protein interactions in living cells using luminescence resonance energy transfer (LRET) from Renilla luciferase to Aequorea GFP , 2001, Molecular and General Genetics MGG.

[78]  Ralph Weissleder,et al.  In vivo molecular target assessment of matrix metalloproteinase inhibition , 2001, Nature Medicine.

[79]  S. Larson,et al.  Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. , 2001, Neoplasia.

[80]  Daniel E. Hall,et al.  Molecular imaging of gene expression and efficacy following adenoviral-mediated brain tumor gene therapy. , 2002, Molecular imaging.

[81]  R. Blasberg,et al.  Imaging expression of cytosine deaminase-herpes virus thymidine kinase fusion gene (CD/TK) expression with [124I]FIAU and PET. , 2002, Molecular imaging.

[82]  Jos Jonkers,et al.  Noninvasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. , 2002, Cancer research.

[83]  D. Piwnica-Worms,et al.  Characterization of a novel 99mTc-carbonyl complex as a functional probe of MDR1 P-glycoprotein transport activity. , 2002, Molecular imaging.

[84]  R. Jain,et al.  Conventional and high-speed intravital multiphoton laser scanning microscopy of microvasculature, lymphatics, and leukocyte-endothelial interactions. , 2002, Molecular imaging.

[85]  A. Szalay,et al.  Imaging of light emission from the expression of luciferases in living cells and organisms: a review. , 2002, Luminescence : the journal of biological and chemical luminescence.

[86]  S S Gambhir,et al.  Noninvasive quantitative imaging of protein–protein interactions in living subjects , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[87]  T. Jacks,et al.  Cancer Modeling in the Modern Era Progress and Challenges , 2002, Cell.

[88]  P. Reynier,et al.  A simple method to overcome the interference of hemoglobin in the detection of reporter genes in vivo. , 2002, Analytical biochemistry.

[89]  Alexander Petrovsky,et al.  Oligomerization of Paramagnetic Substrates Result in Signal Amplification and Can be Used for MR Imaging of Molecular Targets , 2002, Molecular imaging.

[90]  Sanjiv S Gambhir,et al.  Molecular engineering of a two-step transcription amplification (TSTA) system for transgene delivery in prostate cancer. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[91]  G. Woude,et al.  Radioimmunoscintigraphy of tumors autocrine for human met and hepatocyte growth factor/scatter factor. , 2002, Molecular imaging.

[92]  Ivo Que,et al.  Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. , 2002, The American journal of pathology.

[93]  R. Hoffman.  Orthotopic Transplant Mouse Models with Green Fluorescent Protein-expressing Cancer Cells to Visualize Metastasis and Angiogenesis , 1998, Cancer and Metastasis Reviews.