Breast cancer metastasis to bone: evaluation of bioluminescent imaging and microSPECT/CT for detecting bone metastasis in immunodeficient mice

Cowey, Stephanie; Szafran, April Adams; Kappes, John C.; Zinn, Kurt R.; Siegal, Gene P.; Desmond, Reneé A.; Kim, H.; Evans, Lynda M.; Hardy, Robert W.

doi:10.1007/s10585-007-9076-8

Cited by 38 publications

(32 citation statements)

References 16 publications

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“…Small animal imaging with microCT has been applied to monitoring osteolytic lesions under pathological conditions, such as tumor development (Cowey et al 2007; Labrinidis et al, 2009). As bioluminescence imaging of luciferase labeled tumors has been widely adopted pre-clinically, co-registration of bioluminescence and microCT images provided a better definition of anatomical location of the bioluminescence signals (Kaijzel et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Monitoring Tumor Metastases and Osteolytic Lesions with Bioluminescence and Micro CT Imaging

Lim

Modi

Christensen

et al. 2011

JoVE

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Following intracardiac delivery of MDA-MB-231-luc-D3H2LN cells to Nu/Nu mice, systemic metastases developed in the injected animals. Bioluminescence imaging using IVIS Spectrum was employed to monitor the distribution and development of the tumor cells following the delivery procedure including DLIT reconstruction to measure the tumor signal and its location.Development of metastatic lesions to the bone tissues triggers osteolytic activity and lesions to tibia and femur were evaluated longitudinally using micro CT. Imaging was performed using a Quantum FX micro CT system with fast imaging and low X-ray dose. The low radiation dose allows multiple imaging sessions to be performed with a cumulative X-ray dosage far below LD50. A mouse imaging shuttle device was used to sequentially image the mice with both IVIS Spectrum and Quantum FX achieving accurate animal positioning in both the bioluminescence and CT images. The optical and CT data sets were co-registered in 3-dimentions using the Living Image 4.1 software. This multi-mode approach allows close monitoring of tumor growth and development simultaneously with osteolytic activity. Video LinkThe video component of this article can be found at https://www.jove.com/video/2775/ ProtocolLongitudinal imaging is used in pre-clinical studies to follow the progress of a disease or measure the effect of a therapeutic. In oncology, optical methods provide rigorous tools to monitor tumor growth and deliver precise quantitation of cell growth or gene expression at each time point in such a study. Anatomical changes can be measured using a high resolution technique like microCT, but for longitudinal imaging a low X-ray dose must be used to avoid biological artifacts. Optical and microCT images can be co-registered to provide a combination of functional and anatomical data ensuring that maximum information is extracted from the animal model. Cell preparation1. Caliper provides a range of luciferase expressing cancer cell lines for pre-clinical research in mouse models. 2. MDA-MB-231-luc-D2H2LN is a human mammary tumor cell line expressing the luciferase gene which can be used as an optical indicator of tumorgenesis in vivo. This cell line is created from a spontaneous lymph node metastasis that originated from a D3H1 mammary fat pad tumor and is known to aggressively form metastases. 3. The cells are provided as a pathogen-free frozen culture which readily grows in standard media with no need for selection markers. 4. To verify Luciferase activity before injection into the animal a 90% confluent flask is harvested by trypsinization. Luciferase activity is measured by dispensing 50,000 cells in a microtiter plate and performing serial dilution. Intracardiac injection of cells in animals1. Before injection, animals are anesthetized using 3% isoflurane. 2. 1-3 million cells are injected in 50ul volume in to the left ventricle. Cell suspension contains 150ug/ml D-Luciferin to validate injection technique. 3. To confirm a correct intracardiac injection mice are imaged in th...

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Section: Discussionmentioning

confidence: 99%

Monitoring Tumor Metastases and Osteolytic Lesions with Bioluminescence and Micro CT Imaging

Lim

Modi

Christensen

et al. 2011

JoVE

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“…21,47 However, the origin of the cells is uncertain, and it has been suggested that they were derived from a melanoma rather than breast cancer. 62 …”

Section: Animal Modelsmentioning

confidence: 99%

Animal Models of Bone Metastasis

et al. 2015

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Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

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“…Bioluminescence imaging is particularly sensitive for this purpose, as shown in Figure 2. MDA-MB-435 breast cancer cells were induced to express firefly luciferase using a lentiviral vector (as described in Cowey et al 2007) and were administered by intracardiac injection. The image in Figure 2A was collected immediately after injection into the left ventricle and shows the cells in the blood pool.…”

Section: Routine Research Applicationsmentioning

confidence: 99%

Noninvasive Bioluminescence Imaging in Small Animals

Zinn¹,

Chaudhuri²,

Szafran³

et al. 2008

ILAR Journal

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There has been a rapid growth of bioluminescence imaging applications in small animal models in recent years, propelled by the availability of instruments, analysis software, reagents, and creative approaches to apply the technology in molecular imaging. Advantages include the sensitivity of the technique as well as its efficiency, relatively low cost, and versatility. Bioluminescence imaging is accomplished by sensitive detection of light emitted following chemical reaction of the luciferase enzyme with its substrate. Most imaging systems provide 2-dimensional (2D) information in rodents, showing the locations and intensity of light emitted from the animal in pseudo-color scaling. A 3-dimensional (3D) capability for bioluminescence imaging is now available, but is more expensive and less efficient; other disadvantages include the requirement for genetically encoded luciferase, the injection of the substrate to enable light emission, and the dependence of light signal on tissue depth. All of these problems make it unlikely that the method will be extended to human studies. However, in small animal models, bioluminescence imaging is now routinely applied to serially detect the location and burden of xenografted tumors, or identify and measure the number of immune or stem cells after an adoptive transfer. Bioluminescence imaging also makes it possible to track the relative amounts and locations of bacteria, viruses, and other pathogens over time. Specialized applications of bioluminescence also follow tissue-specific luciferase expression in transgenic mice, and monitor biological processes such as signaling or protein interactions in real time. In summary, bioluminescence imaging has become an important component of biomedical research that will continue in the future.

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Breast cancer metastasis to bone: evaluation of bioluminescent imaging and microSPECT/CT for detecting bone metastasis in immunodeficient mice

Cited by 38 publications

References 16 publications

Monitoring Tumor Metastases and Osteolytic Lesions with Bioluminescence and Micro CT Imaging

Monitoring Tumor Metastases and Osteolytic Lesions with Bioluminescence and Micro CT Imaging

Animal Models of Bone Metastasis

Noninvasive Bioluminescence Imaging in Small Animals

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