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ABSTRACT: Bioluminescent imaging (BLI) is a non-invasive imaging modality widely used in the field of pre-clinical oncology research. Imaging of small animal tumour models using BLI involves the generation of light by luciferase-expressing cells in the animal following administration of substrate. This light may be imaged using an external detector. The technique allows a variety of tumour-associated properties to be visualized dynamically in living models. The increasing use of BLI as a small-animal imaging modality has led to advances in the development of xenogeneic, orthotopic, and genetically engineered animal models expressing luciferase genes. This review aims to provide insight into the principles of BLI and its applications in cancer research. Many studies to assess tumour growth and development, as well as efficacy of candidate therapeutics, have been performed using BLI. More recently, advances have also been made using bioluminescent imaging in studies of protein-protein interactions, genetic screening, cell-cycle regulators, and spontaneous cancer development. Such novel studies highlight the versatility and potential of bioluminescent imaging in future oncological research.
The Journal of Pathology 10/2009; 220(3):317-27. · 6.32 Impact Factor
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Scott K Lyons,
Ed Lim,
Anne O Clermont,
Joan Dusich,
Lingyun Zhu,
Kenneth D Campbell,
Richard J Coffee,
David S Grass,
John Hunter,
Tony Purchio,
Darlene Jenkins
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ABSTRACT: Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.
Cancer Research 06/2006; 66(9):4701-7. · 7.86 Impact Factor
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Scott K Lyons
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ABSTRACT: Significant progress has been made recently in the variety of ways that cancer can be non-invasively imaged in murine tumour models. The development and continued refinement of specialized hardware for an array of small animal imaging methodologies are only partly responsible. So too has been the development of new imaging techniques and materials that enable specific, highly sensitive and quantitative measurement of a wide range of tumour-related parameters. Included amongst these new materials are imaging probes that selectively accumulate in tumours, or that become activated by tumour-specific molecules in vivo. Other tumour imaging strategies have been developed that rely upon the detection of reporter transgene expression in vivo, and these too have made a significant impact on both the versatility and the specificity of tumour imaging in living mice. The biological implications resulting from these latest advances are presented here, with particular emphasis on those associated with MRI, PET, SPECT, BLI, and fluorescence-based imaging modalities. Taken together, these advances in tumour imaging are set to have a profound impact on our basic understanding of in vivo tumour biology and will radically alter the application of mouse tumour models in the laboratory.
The Journal of Pathology 02/2005; 205(2):194-205. · 6.32 Impact Factor
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ABSTRACT: The ability to noninvasively quantitate tumor burden from conditional (Cre/loxP-dependent) mouse cancer models would greatly increase their range of useful applications. We now report the generation of a reporter mouse that enables visualization of spontaneous tumor development from pre-existing conditional mouse tumor models via in vivo bioluminescence imaging. We demonstrate that bioluminescence can be "switched-on" in a Cre-dependent manner in every organ analyzed, and that this gives rise to between a 4 and 6-log increase in light emission per mg of wet tissue weight. Furthermore, we highlight the utility of this reporter by showing that it can be used as a sensitive means to measure spontaneous Kras2(v12)-induced lung tumorigenesis in a pre-existing mouse model of non-small cell lung cancer. Taken together, our results suggest that this reporter may be combined with a wide-range of other Cre/loxP tumor mouse models, irrespective of their tissue specificity and render them immediately amenable to longitudinal monitoring of tumor growth and therapeutic response with a noninvasive in vivo imaging approach.
Cancer Research 12/2003; 63(21):7042-6. · 7.86 Impact Factor
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ABSTRACT: Many tumours are charcterised by increased levels of apoptosis. This observation establishes significance for this process in tumour development, but it does little to elucidate the nature of this role, nor does if yield information relevant to the early stages of carcionognesis. To gain a better understanding of the improtance of apoptosis, it has been necessary to create a number of transgenic model systems wherein the apoptotic response has been modified. Usaing this strategy, a number of genetic lesions have been identified which affect both the apoptotic pathway and predisposition to malignancy. These lesions can operate either directly, by blocking the induction of apoptosis; or indirectly, by increasing the selective pressure for further genetic change. The consequent deregulation of growth control and increase in mutation burden represent two key steps in carcinogenesis, underlining the pivotal role played in tunmour suppression by the normal induction of opoptosis.
