In vivo imaging using bioluminescence: a tool for probing graft-versus-host disease

Department of Medicine, Center for Clinical Research Building, 269 West Campus Drive, Stanford University, Stanford, California 94305, USA.
Nature reviews. Immunology (Impact Factor: 33.84). 07/2006; 6(6):484-90. DOI: 10.1038/nri1879
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Christopher H Contag, Aug 21, 2015
  • Source
    • "The excitation and emission wavelengths used in this study to detect abdominal accumulation were >600 nm. Longer wavelengths of bioluminescence in the red and near-infrared regions of the spectrum are transmitted through mammalian tissues more efficiently than are shorter wavelengths of light [45]. A significant fluorescence signal was observed in the abdominal region of rats treated with NLCs containing Myverol (M3). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanostructured lipid carriers (NLCs) made from mixtures of Precirol and squalene were prepared to investigate whether the bioavailability of lovastatin can be improved by oral delivery. The size, zeta potential, drug-loading capacity, and release properties of the NLCs were compared with those of lipid nanoparticles containing pure Precirol (solid lipid nanoparticles, SLNs) and squalene (lipid emulsions, LEs). Stable nanoparticles with a mean size range of 180-290 nm and zeta potential range of -3 to -35 mV were developed. More than 70% lovastatin was entrapped in the NLCs and LEs, which was significantly higher compared to the SLNs. The in vitro release kinetics demonstrated that lovastatin release could be reduced by up to 60% with lipid nanoparticles containing Myverol as the lipophilic emulsifier, which showed a decreasing order of NLCs>LEs>SLNs. Drug release was further decreased by soybean phosphatidylcholine (SPC) incorporation, with NLCs and SLNs showing the slowest delivery. The oral lovastatin bioavailability was enhanced from 4% to 24% and 13% when the drug was administered from NLCs containing Myverol and SPC, respectively. The in vivo real-time bioluminescence imaging indicated superior stability of the Myverol system over the SPC system in the gastric environment.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 03/2010; 74(3):474-82. DOI:10.1016/j.ejpb.2009.12.008 · 4.25 Impact Factor
  • Source
    • "These technologies are currently mostly used in laboratory studies but, in their current state of development, cannot realistically be applied to humans. The most widely used technique is bioluminescence imaging, which relies on the detection of light emitted by oxidation of the luciferin substrate upon catalysis by the luciferase enzyme (Sweeney et al., 1999; Negrin and Contag, 2006). This reaction requires ATP, magnesium and oxygen. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Biotherapies involve the utilization of antibodies, genetically modified viruses, bacteria or cells for therapeutic purposes. Molecular imaging has the potential to provide unique information that will guarantee their biosafety in humans and provide a rationale for the future development of new generations of reagents. In this context, non-invasive imaging of gene expression is an attractive prospect, allowing precise, spacio-temporal measurements of gene expression in longitudinal studies involving gene transfer vectors. With the emergence of cell therapies in regenerative medicine, it is also possible to track cells injected into subjects. In this context, the Na/I symporter (NIS) has been used in preclinical studies. Associated with a relevant radiotracer ((123)I(-), (124)I(-), (99m)TcO4(-)), NIS can be used to monitor gene transfer and the spread of selectively replicative viruses in tumours as well as in cells with a therapeutic potential. In addition to its imaging potential, NIS can be used as a therapeutic transgene through its ability to concentrate therapeutic doses of radionuclides in target cells. This dual property has applications in cancer treatment and could also be used to eradicate cells with therapeutic potential in the case of adverse events. Through experience acquired in preclinical studies, we can expect that non-invasive molecular imaging using NIS as a transgene will be pivotal for monitoring in vivo the exact distribution and pharmacodynamics of gene expression in a precise and quantitative way. This review highlights the applications of NIS in biotherapy, with a particular emphasis on image-guided radiotherapy, monitoring of gene and vector biodistribution and trafficking of stem cells.
    British Journal of Pharmacology 10/2009; 159(4):761-71. DOI:10.1111/j.1476-5381.2009.00412.x · 4.99 Impact Factor
  • Source
    • "Most studies turn to profit the large number of insects, bacteria and marine animals expressing luminescent proteins, which are absent in mammalians. The injection of luminescent cells into an animal [6], or the expression luminescent proteins in a cell [7] provides a signal detectable with a high specificity. Specific photoproteins can probe calcium ions (aequorin), nicotinamide adenine dinucleotide (bacterial luciferase), superoxide free radicals (lucigenin) or adenosine triphosphate (ATP) (firefly luciferase). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Algol and Comptage de Photons Nouvelle Génération (CPNG) are new generation photon counting cameras developed for high angular resolution in the visible by means of optical aperture synthesis and speckle interferometry and for photon noise limited fast imaging of biological targets. They are intensified CCDs. They have been built to benefit from improvements in photonic commercial components, sensitivity, and personal computer workstations processing power. We present how we achieve optimal performances (sensitivity and spatiotemporal resolution) by the combination of proper optical and electronics design, and real-time elaborated data processing. The number of pixels is 532 x 516 and 1024(2) read at a frame rate of 262 and 100 Hz for CPNG and Algol, respectively. The dark current is very low: 5.5 x 10(-4) e(-) .pixel(-1). s(-1). The saturation flux is approximately 7 photon events /pixel/s. Quantum efficiencies reach up to 36% and 26% in the visible with the GaAsP photocathodes and in the red with the GaAs ones, respectively, thanks to the sensitivity of the photocathodes and to the photon centroiding algorithm; they are likely the highest values reported for intensified CCDs.
    Applied Optics 04/2008; 47(8):1141-51. DOI:10.1364/AO.47.001141 · 1.78 Impact Factor
Show more