<i>In vivo</i>positron-emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia

Abbey, Craig K.; Borowsky, Alexander D.; McGoldrick, Erik T.; Gregg, Jeffrey P.; Maglione, Jeannie E.; Cardiff, Robert D.; Cherry, Simon R.

doi:10.1073/pnas.0404396101

Cited by 54 publications

(47 citation statements)

References 20 publications

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“…Previously, micro-PET imaging has been useful to study the growth and tumor progression of the MIN-Os (26). The MIN-Otransplanted animals were imaged using micro-PET weekly for 3 weeks, starting just before the beginning of the treatment (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We chose to evaluate the effects of rapamycin in vivo using the small-animal PET imaging technique previously shown to discriminate premalignant from malignant tissue in the MIN-O model (26). Animals were scanned on a dedicated small-animal PET scanner (micro-PET Focus system, CTI Concorde, Knoxville, TN) using the glucose analogue 2-[ List-mode scanner data was converted to a sinogram and then reconstructed using an iterative maximum a posteriori reconstruction algorithm (27,28).…”

Section: In Vivo Imaging Techniquesmentioning

confidence: 99%

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Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma In situ

Namba¹,

Young²,

Abbey

et al. 2006

Clinical Cancer Research

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Purpose: Rapamycin has been shown to have antitumor effects in various tumor models.To study the effect of rapamycin at different stages of breast cancer development, we used two unique mouse models of breast cancer with activated phosphatidylinositol 3-kinase (PI3K) pathway. Met-1 tumors are highly invasive and metastatic, and mammary intraepithelial neoplasiaoutgrowths (MIN-O), a model for human ductal carcinoma in situ, are transplantable premalignant mammary lesions that develop invasive carcinoma with predictable latencies. Both of these models were derived from mammary lesions inTg(MMTV-PyV-mT) mice. Experimental Design: Met-1tumors were used to study the effect of rapamycin treatment on invasive disease.Transplanted MIN-O model was used to study the effect of rapamycin on premalignant mammary lesions. Animals were in vivo micro^positron emission tomography imaged to follow the lesion growth and transformation to tumor during the treatment. Cell proliferation, angiogenesis, and apoptosis was assayed by immunohistochemistry. Results: Rapamycin inhibited in vitro tumor cell proliferation and in vivo Met-1tumor growth.The growth inhibition was correlated with dephosphorylation of mammalian target of rapamycin (mTOR) targets. Rapamycin treatment significantly reduced the growth of the premalignant MIN-O lesion, as well as tumor incidence and tumor burden. Growth inhibition was associated with reduced cell proliferation and angiogenesis and increased apoptosis. Conclusions: In PyV-mT mouse mammary models, rapamycin inhibits the growth of premalignant lesions and invasive tumors. Although the inhibitory effect of rapamycin was striking, rapamycin treatment did not completely obliterate the lesions.

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Section: Resultsmentioning

confidence: 99%

Section: In Vivo Imaging Techniquesmentioning

confidence: 99%

Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma In situ

Namba¹,

Young²,

Abbey

et al. 2006

Clinical Cancer Research

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“…In Fig.1a, this template was overlaid on the atlas. All ROI volumes were within the resolution of maximum likelihood-expectation maximization (MLEM) reconstructed microPET data (5 mm 3 or ~5μl (Abbey et al, 2004) at the center of the field of view and based on a 10nsec timing window). The center coordinates and volumes for each region are reported in Table 1.…”

Section: Region Of Interest (Roi) Templatementioning

confidence: 99%

A novel approach for imaging brain–behavior relationships in mice reveals unexpected metabolic patterns during seizures in the absence of tissue plasminogen activator

et al. 2007

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Medically-refractory seizures cause inflammation and neurodegeneration. Seizure initiation thresholds have been linked in mice to the serine protease tissue plasminogen activator (tPA); mice lacking tPA exhibit resistance to seizure induction, and the ensuing inflammation and neurodegeneration are similarly suppressed. Seizure foci in humans can be examined using PET employing 2-deoxy-2[ 18 F]fluoro-D-glucose ( 18 FDG) as a tracer to visualize metabolic dysfunction. However, there currently exist no such methods in mice to correlate measures of brain activation with behaviour. Using a novel method for small animal PET data analysis, we examine patterns of 18 FDG uptake in wild type and tPA -/-mice and find that they correlate with the severity of druginduced seizure initiation. Furthermore, we report unexpected activations that may underlie the tPA modulation of seizure susceptibility. The methods described here should be applicable to other mouse models of human neurological disease.

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“…Metabolic imaging is an example where 2[ 18 F]-fluoro-deoxy-Dglucose probes sensed by PET scanners generate high object contrast by exploiting the large differential uptake of the glucose probe into cancer cells. PET imaging has been found to provide quantitative information that correlates well with histological features describing the progression of ductal carcinoma in situ (DCIS) to infiltrating ductal carcinoma (IDC) in breast cancer mouse models (9).…”

Section: Introductionmentioning

confidence: 99%

Viscoelastic Imaging of Breast Tumor Microenvironment With Ultrasound

Insana

Pellot‐Barakat

Sridhar

et al. 2004

J Mammary Gland Biol Neoplasia

100

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Imaging systems are most effective for detection and classification when they exploit contrast mechanisms specific to particular disease processes. A common example is mammography, where the contrast depends on local changes in cell density and the presence of microcalcifications. Unfortunately the specificity for classifying malignant breast disease is relatively low for many current diagnostic techniques. This paper describes a new ultrasonic technique for imaging the viscoelastic properties of breast tissue. The mechanical properties of glandular breast tissue, like most biopolymers, react to mechanical stimuli in a manner specific to the microenvironment of the tissue. Elastic properties allow noninvasive imaging of desmoplasia while viscous properties describe metabolism-dependent features such as pH. These ultrasonic methods are providing new tools for studying disease mechanisms as well as improving diagnosis.

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In vivopositron-emission tomography imaging of progression and transformation in a mouse model of mammary neoplasia

Cited by 54 publications

References 20 publications

Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma In situ

Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma In situ

A novel approach for imaging brain–behavior relationships in mice reveals unexpected metabolic patterns during seizures in the absence of tissue plasminogen activator

Viscoelastic Imaging of Breast Tumor Microenvironment With Ultrasound

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