Visualization of Inflammation at Early Stage of Lung Cancer in Xenografted Temporally Immunosuppression Rats by Ferrioxamine Magnetic Resonance Imaging (original) (raw)

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

PloS one, 2016

Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections. Th...

Detection of Primary Lung Tumors in Rodents by Magnetic Resonance Imaging

Cancer Research, 2004

This report describes recent efforts to develop and apply small animal magnetic resonance imaging methods to the study of lung tumors in mice. Magnetic resonance (MR) images obtained with respiratory gating, with data collection synchronized with the respiration of the animal, allow visualization of submillimeter tumors in animals treated with a lung carcinogen. Comparison of the MR images with gross pathology of these lungs demonstrates the utility of the imaging methods for measuring tumor burden. As a noninvasive imaging modality that uses nonionizing radiation, MR is well suited to longitudinal studies aimed at understanding the factors that control the onset and development of lung tumors and their response to therapy in a wide variety of animal models.

Molecular Imaging of Inflammation and Carcinogenesis

Cancer Prevention Research, 2011

Development of imaging agents that can be used broadly for early detection of neoplasia at various tissue sites and at various stages of disease and that also can assess states of minimal residual disease would have tremendous utility in the diagnosis and management of cancer. In a series of articles culminating with a report in this issue of the journal (beginning on page 1536), Uddin and colleagues show their ability to systemically target the enzyme COX-2 with imaging probes that will serve as agents for early detection, risk assessment, prognosis, and intervention outcome measures. These probes will enable the detection and localization of regions of inflammation and a wide variety of premalignant lesions and cancers, with utility in monitoring the effects of cancer prevention and therapy. Cancer Prev Res; 4(10); 1523-6. Ó2011 AACR.

The role of magnetic resonance imaging in oncology

Clinical and Translational Oncology, 2010

Conventional diagnostic magnetic resonance imaging (MRI) techniques have focused on improving the spatial resolution and image acquisition speed (whole-body MRI) or on new contrast agents. Most advances in MRI go beyond morphologic study to obtain functional and structural information in vivo about different physiological processes of tumor microenvironment, such as oxygenation levels, cellular proliferation, or tumor vascularization through MRI analysis of some characteristics: angiogenesis (perfusion MRI), metabolism (MRI spectroscopy), cellularity (diffusion-weighted MRI), lymph node function, or hypoxia [blood-oxygen-level-dependent (BOLD) MRI]. We discuss the contributions of different MRI techniques than must be integrated in oncologic patients to substantially advance tumor detection and characterization risk stratification, prognosis, predicting and monitoring response to treatment, and development of new drugs.

Early detection of lung inflammation: Exploiting T 1 -effects of iron oxide particles using UTE MRI

Magnetic Resonance in Medicine, 2012

At high magnetic fields diagnostic proton MRI of the lung is problematic, because of fast T 2 * relaxation. The application of superparamagnetic contrast agents and the exploitation of the corresponding T 2 * effect is inefficient with conventional MRI methods, which limits the early detection of lung diseases. However, a simple theoretical treatment shows that in the lung, by the use of ultra-short echo time sequences, T 2 * effects can be neglected while T 1 shortening effects can be used for signal detection. In our study, we have applied a theoretically and experimentally optimized 3D ultra-short echo time sequence to lung phantoms and to a mouse model of lung inflammation, which was induced by systemic bacterial infection. Following the systemic application of very small superparamagnetic iron oxide nanoparticles, a significant signal increase in the lung of infected animals was detected already at 24 h postinfection, compared to control mice (17%, P < 0.001). Iron accumulation in the lung parenchyma as consequence of the host immune response was histologically confirmed. By conventional T 2 *-and T 2-weighted imaging, neither structural changes nor formation of substantial edema were observed. Magn Reson Med 000:000-000, 2012.

MRI detection of tumor in mouse lung using partial liquid ventilation with a perfluorocarbon-in-water emulsion

Magnetic Resonance Imaging, 2004

Transverse relaxation time (T* 2)-weighted 1 H-MRI of mouse lungs has been performed using partial liquid ventilation (PLV) with a perfluorocarbon (PFC)-in-water emulsion as a contrast modality for lung MRI. Significant sensitivity enhancement in MRI of mouse lungs has been demonstrated with the protocol. The results show that the T* 2 value in lung is approximately proportional to the infusion dose up to a dose of 5 ml/kg body weight (BW) (4.5 g PFC/kg BW) and becomes essentially constant beyond this dosage. T* 2 maps of lungs have been calculated and T* 2 in lungs is in the range of 10-35 ms with this technique, which is an order of magnitude greater than the T* 2 value of mouse lungs without using a PFC-in-water emulsion. T* 2-weighted 1 H-MR images of mouse lungs have been obtained with good quality under our experimental conditions. We have applied this technique to detect tumors in mouse lungs. Our technique can detect small lung tumors of B16 melanoma, about 1 mm in diameter, in mice. With its significant MR sensitivity enhancement and technical simplicity, T* 2-weighted 1 H-MRI using PLV with PFC-in-water emulsion offers a promising approach to investigate lung cancers using rodent models.

Quantitative monitoring of mouse lung tumors by magnetic resonance imaging

Nature Protocols, 2012

primary lung cancer remains the leading cause of cancer-related death in the Western world, and the lung is a common site for recurrence of extrathoracic malignancies. small-animal (rodent) models of cancer can have a very valuable role in the development of improved therapeutic strategies. However, detection of mouse pulmonary tumors and their subsequent response to therapy in situ is challenging. We have recently described MrI as a reliable, reproducible and nondestructive modality for the detection and serial monitoring of pulmonary tumors. By combining respiratory-gated data acquisition methods with manual and automated segmentation algorithms described by our laboratory, pulmonary tumor burden can be quantitatively measured in approximately 1 h (data acquisition plus analysis) per mouse. Quantitative, analytical methods are described for measuring tumor burden in both primary (discrete tumors) and metastatic (diffuse tumors) disease. thus, small-animal MrI represents a novel and unique research tool for preclinical investigation of therapeutic strategies for treatment of pulmonary malignancies, and it may be valuable in evaluating new compounds targeting lung cancer in vivo. protocol 130 | VOL.7 NO.1 | 2012 | nature protocols protocol 132 | VOL.7 NO.1 | 2012 | nature protocols protocol 138 | VOL.7 NO.1 | 2012 | nature protocols

Molecular Imaging of Angiogenesis in Nascent Vx-2 Rabbit Tumors Using a Novel 3-targeted Nanoparticle and 1.5 Tesla Magnetic Resonance Imaging 1

Early noninvasive detection and characterization of solid tumors and their supporting neovasculature is a fundamental prerequisite for effective therapeutic intervention, particularly antiangiogenic treatment regimens. Emerging molecular imaging techniques now allow recognition of early biochemical, physiological, and anatomical changes before manifestation of gross pathological changes. Although new tumor, vascular, extracellular matrix, and lymphatic biomarkers continue to be discovered, the ␣ ␤ 3 -integrin remains an attractive biochemical epitope that is highly expressed on activated neovascular endothelial cells and essentially absent on mature quiescent cells. In this study, we report the first in vivo use of a magnetic resonance (MR) molecular imaging nanoparticle to sensitively detect and spatially characterize neovascularity induced by implantation of the rabbit Vx-2 tumor using a common clinical field strength (1.5T). New Zealand White rabbits (2 kg) 12 days after implantation of fresh Vx-2 tumors (2 ؋ 2 ؋ 2 mm 3 ) were randomized into one of three treatment groups: (a) ␣ ␤ 3 -targeted, paramagnetic formulation; (b) nontargeted, paramagnetic formulation; and (c) ␣ ␤ 3 -targeted nonparamagnetic nanoparticles followed by (2 h) the ␣ ␤ 3 -targeted, paramagnetic formulation to competitively block magnetic resonance imaging (MRI) signal enhancement. After i.v. systemic injection (0.5 ml of nanoparticles/kg), dynamic T 1 -weighted MRI was used to spatially and temporally determine nanoparticle deposition in the tumor and adjacent tissues, including skeletal muscle. At 2-h postinjection, ␣ ␤ 3 -targeted paramagnetic nanoparticles increased MRI signal by 126% in asymmetrically distributed regions primarily in the periphery of the tumor. Similar increases in MR contrast were also observed within the walls of some vessels proximate to the tumor. Despite their relatively large size, nanoparticles penetrated into the leaky tumor neovasculature but did not appreciably migrate into the interstitium, leading to a 56% increase in MR signal at 2 h. Pretargeting of the ␣ ␤ 3 -integrin with nonparamagnetic nanoparticles competitively blocked the specific binding of ␣ ␤ 3 -targeted paramagnetic nanoparticles, decreasing the MR signal enhancement (50%) to a level attributable to local extravasation. The MR signal of adjacent hindlimb muscle or contralateral control tissues was unchanged by either the ␣ ␤ 3 -targeted or control paramagnetic agents. Immunohistochemistry of ␣ ␤ 3 -integrin corroborated the extent and asymmetric distribution of neovascularity observed by MRI. These studies demonstrate the potential of this targeted molecular imaging agent to detect and characterize (both biochemically and morphologically) early angiogenesis induced by minute solid tumors with a clinical 1.5 Tesla MRI scanner, facilitating the localization of nascent cancers or metastases, as well as providing tools to phenotypically categorize and segment patient populations for therapy and to longitudinally follow the effectiveness of antitumor treatment regimens.