Advances in bioluminescence imaging of live animal models

Dothager, Robin S.; Flentie, Kelly; Moss, Britney L.; Pan, Michael; Kesarwala, Aparna H.; Piwnica‐Worms, David

doi:10.1016/j.copbio.2009.01.007

Cited by 127 publications

(116 citation statements)

References 42 publications

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“…[25][26][27][28][29][30] Luciferase reporters provide great sensitivity because of the extremely low background luminescence in wild-type animals and represent a broadly applicable approach to noninvasive disease monitoring. [31][32][33] Firefly luciferase is particularly versatile as a bioluminescent reporter, as a significant portion of its emission spectrum is Ͼ 600 nm, wavelengths that achieve good tissue penetrance. 34 Although these reporters require introduction of a novel substrate to achieve luminescence, the 2 most common substrates for bioluminescent reporters, luciferin and colenterazine, are well tolerated by animals.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling

Barrett

Seif

Carpenito

et al. 2011

Blood

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The efficient engraftment in immunedeficient mice achieved with both acute lymphoblastic leukemia (ALL) cell lines and primary samples has facilitated identification of the antileukemia activity of a wide variety of agents. Despite widespread usage, however, little is known about the early ALL localization and engraftment kinetics in this model, limiting experimental read-outs primarily to survival and endpoint analysis at high disease burden. In this study, we report that bioluminescent imaging can be reproducibly achieved with primary human ALL samples. This approach provides a noninvasive, longitudinal measure of leukemia burden and localization that enhances the sensitivity of treatment response detection and provides greater insight into the mechanism of action of antileukemia agents. In addition, this study reveals significant cell line-and species-related differences in leukemia migration, especially early in expansion, which may confound observations between various leukemia models. Overall, this study demonstrates that the use of bioluminescent primary ALL allows the detection and quantitation of treatment effects at earlier, previously unquantifiable disease burdens and thus provides the means to standardize and expedite the evaluation of anti-ALL activity in preclinical xenograft studies. (Blood. 2011;118(15): e112-e117) IntroductionMurine leukemia models have been useful and versatile tools for identifying and targeting underlying disease mechanisms. 1 However, preclinical studies involving human samples are more immediately applicable when investigating new drugs or therapies. Initial studies with human leukemia in immune-deficient mice, such as the NOD/SCID (NOD.CB17-Prkdc scid /J), were a great step forward and remain valuable for rapid iterations in the study of novel therapies at the preclinical level. 2,3 More recently, use of severely immune-deficient NOD/SCID/␥c Ϫ/Ϫ (NSG; NOD.Cg-Prkdc scid / IL2rg tm1Wjl /SzJ and NOG; NOD.Cg-Prkdc scid /Il2rgt m1Sug /Jic) mice, which lack functional B, T, and NK cells, has allowed for more consistent and reproducible engraftment of normal human cells and primary leukemias. [4][5][6] Primary acute lymphoblastic leukemia (ALL) xenografts in immune-deficient mice accurately represent human disease and gene expression and may have predictive value for clinical variables, such as drug resistance and time to relapse. [7][8][9][10][11] Although this model is a powerful and widely used tool for the ongoing development of new drugs and biologic therapeutics for ALL, [12][13][14][15][16][17][18][19] the kinetics of every primary patient sample are different, some engrafting in 4 weeks and others taking as long as one year, when measured by the appearance of human ALL blasts in peripheral blood. 5,10,20 The endpoints of these studies are typically limited to survival analysis and time to grossly detectable disease. Monitoring the peripheral blood compartment for blasts is the primary method of disease detection, leaving the early engraftment kinetics and localization, t...

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Section: Introductionmentioning

confidence: 99%

Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling

Barrett

Seif

Carpenito

et al. 2011

Blood

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“…The shortcoming of using BLI is the limit of penetration depth to *1 cm, which makes it practical for only small-animal imaging (Choy et al, 2003;Dothager et al, 2009). Using an enhanced firefly luciferase (eLuc) (Rabinovich et al, 2008), we can visualize as few as five HCT116 cells transduced with VSV-G-pseudotyped SIV mac239 -eLuc (Fig.…”

Section: Discussionmentioning

confidence: 99%

Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

Song

Cai

White

et al. 2015

Journal of General Virology

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In vivo imaging can provide real-time information and three-dimensional (3D) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. Current in vivo imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint the spatial location of target cells, which is urgently needed for revealing human immunodeficiency virus (HIV) dissemination in real-time and HIV-1 reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that in vivo imaging can be used to visualize and quantify simian immunodeficiency virus (SIV)-transduced cells, we genetically engineered SIV to carry different imaging reporters. Based on the expression of the reporter genes, we could visualize and quantify the SIV-transduced cells via vesicular stomatitis virus glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also engineered a chimeric EcoSIV for in vivo infection study. Our results demonstrated that BLI is sensitive enough to detect as few as five single cells transduced with virus, whilst PET-CT can provide 3D images of the spatial location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI can provide images with high spatial resolution in a 3D anatomical context to distinguish a small population of SIV-transduced cells. The in vivo imaging platform described here can potentially serve as a powerful tool to visualize lentiviral infection, including when and where viraemia rebounds, and how reservoirs are formed and maintained during latency or suppressive ART.

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“…1 In particular, the luciferase reporter has many clinical, diagnostic, and drug discovery applications, and it is frequently used to monitor noninvasively in vivo biological processes, such as gene expression, protein-protein interaction, and disease progression in living tissues, cells, and animal models. [2][3][4] Noninvasive optical monitoring including bioluminescence imaging (BLI) requires the light emitted in the body to overcome tissue attenuation, which is usually greater below a wavelength of 600 nm. [5][6] For this reason, red-emitting luciferases are considered advantageous for BLI.…”

Section: Introductionmentioning

confidence: 99%

Enhanced red‐emitting railroad worm luciferase for bioassays and bioimaging

Nakajima

Niwa

et al. 2009

Protein Science

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A luciferase from the railroad worm (Phrixothrix hirtus) is the only red-emitting bioluminescent enzyme in nature that is advantageous in multicolor luciferase assays and in bioluminescence imaging (BLI). However, it is not used widely in scientific or industrial applications because of its low activity and stability. By using site-directed mutagenesis, we produced redemitting mutants with higher activity and better stability. Compared with the wild-type (WT), the luminescent activities from extracts of cultured mammalian cells expressing mutant luciferase were 9.8-fold in I212L/N351K, 8.4-fold in I212L, and 7.8-fold in I212L/S463R; and the cell-based activities were 3.6-fold in I212L/N351K and 3.4-fold in N351K. The remaining activities after incubation at 37°C for 10 min were 50.0% for I212L/S463R, 31.8% for I212L, and 23.0% for I212L/ N351K, but only 5.2% for WT. To demonstrate an application of I212L/N351K, cell-based BLI was performed, and the luminescence signal was 3.6-fold higher than in WT. These results indicate that the mutants might improve the practicability of this signaling in bioassays and BLI.

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Advances in bioluminescence imaging of live animal models

Cited by 127 publications

References 42 publications

Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling

Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling

Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

Enhanced red‐emitting railroad worm luciferase for bioassays and bioimaging

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