Passage of DMP Across a Disrupted BBB in the Context of Antibody-mediated MR Imaging of Brain Metastases

Bulte, Jeff W.M.; Jonge, M. W. A. de; Leij, Lou de; Kamman, R. L.; Blaauw, Bert; Zuiderveen, F.; Go, K.G.

doi:10.1007/978-3-7091-9115-6_15

Cited by 5 publications

(5 citation statements)

References 3 publications

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“…Bulte at al. (17) used a freezing lesion to induce disruption of the BBB. In that model, systemically injected dextran‐magnetite particles (DMPs) were observed in endothelial cells within the lesion.…”

Section: Discussionmentioning

confidence: 99%

MRI‐based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE

Rausch

Hiestand

Baumann

et al. 2003

Magnetic Resonance in Med

150

117

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Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model that in several respects mimics human multiple sclerosis (MS), and can be used to design or validate new strategies for treatment of this disease. In the present study, different MRI techniques (macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), blood-brain barrier (BBB) breakdown, and magnetization transfer imaging (MTI)), as well as immunohistological staining were used to study the burden of disease in Lewis rats immunized by guinea pig myelin. The resulting imaging data was compared with behavioral readouts. Animals were studied during the acute phase and the first relapse. Activated monocytes were detected during both episodes in the brain stem or cortex. These areas coincided in part with areas of BBB breakdown. Significant changes of the magnetization transfer ratios (MTRs) of up to 35% were observed in areas of USPIO accumulation. This suggests that infiltrating monocytes are the major source of demyelination in EAE, but monocyte infiltration and breakdown of the BBB are temporally or spatially independent inflammatory processes. Magn Reson Med 50:309 -314, 2003.

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Section: Discussionmentioning

confidence: 99%

MRI‐based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE

Rausch

Hiestand

Baumann

et al. 2003

Magnetic Resonance in Med

150

117

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“…MRI has been used to image SPIO-conjugated antibodies or antibody fragments in diagnostics (2, 5, 9, 19, 27, 32, 35, 38, 39), imaging of transgene expression (31), and cell tracking (6, 22). Exploiting the biotin-streptavidinavidin interactions, cells have been labeled for MRI by binding of streptavidin or avidin conjugated to SPIOs or gadolinium chelates to endogenous surface antigens (e.g., the Her-2/neu and tissue factor receptors) (2, 3, 23).…”

Section: Discussionmentioning

confidence: 99%

Efficient and Rapid Labeling of Transplanted Cell Populations with Superparamagnetic Iron Oxide Nanoparticles Using Cell Surface Chemical Biotinylation for in Vivo Monitoring by MRI

Kalber

Hunt

et al. 2010

Cell Transplant

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Determination of the dynamics of specific cell populations in vivo is essential for the development of cellbased therapies. For cell tracking by magnetic resonance imaging (MRI), cells need to internalize, or be surface labeled with a MRI contrast agent, such as superparamagnetic iron oxide nanoparticles (SPIOs): SPIOs give rise to signal loss by gradient-echo and T 2 -weighted MRI techniques. In this study, cancer cells were chemically tagged with biotin and then magnetically labeled with anti-biotin SPIOs. No significant detrimental effects on cell viability or death were observed following cell biotinylation. SPIO-labeled cells exhibited signal loss compared to non-SPIO-labeled cells by MRI in vitro. Consistent with the in vitro MRI data, signal attenuation was observed in vivo from SPIO-labeled cells injected into the muscle of the hind legs, or implanted subcutaneously into the flanks of mice, correlating with iron detection by histochemical and X-ray fluorescence (XRF) methods. To further validate this approach, human mesenchymal stem cells (hMSCs) were also employed. Chemical biotinylation and SPIO labeling of hMSCs were confirmed by fluorescence microscopy and flow cytometry. The procedure did not affect proliferation and multipotentiality, or lead to increased cell death. The SPIO-labeled hMSCs were shown to exhibit MRI signal reduction in vitro and was detectable in an in vivo model. In this study, we demonstrate a rapid, robust, and generic methodology that may be a useful and practical adjuvant to existing methods of cell labeling for in vivo monitoring by MRI. Further, we have shown the first application of XRF to provide iron maps to validate MRI data in SPIO-labeled cell tracking studies.Key words: Magnetic resonance imaging (MRI); Cell labeling; Chemical biotinylation; Superparamagnetic iron oxide nanoparticles (SPIOs) INTRODUCTIONtracking in vivo [reviewed in (6,22)]. Contrast agents include those based on superparamagnetic iron oxide nanoparticles (SPIOs), which predominantly enhance T 2 The monitoring of specific cell populations is essential for understanding their role in health and disease, relaxation and range from micron size to nanometer size. Labeling of cells for MRI monitoring usually involves and also for the development of cell-based therapies (11,28,36,42). Until relatively recently, tracking particuinternalization of contrast agents, with or without assistance from, for example, polycationic compounds or lar cell populations in vivo has not been possible, such information being derived only from ex vivo histology.translocating peptides (20,33). Alternatively, cells have been tracked in vivo by surface labeling of cells using Magnetic resonance imaging (MRI) is a commonly employed noninvasive imaging modality and cells have cell-specific antibodies that are also conjugated to contrast agents (1 Chemical biotinylation of cells involve reaction of line) were cultured in Dulbecco's modified Eagle's medium (DMEM, Sigma-Aldrich Co. Ltd., Poole, UK) supthe N-hydroxysuccinimide (NHS) este...

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“…Disrupting the BBB using the freezing lesion model, dextran-coated iron oxide (approximately 50 nm in size) was detected in endothelial cells on electron microscopy after 1 hour and persisted for 4–8 hours. On MRI, iron oxide enhancement was seen consistent with BBB breakdown [ 175 ]. After opening the BBB with mannitol, both MION (size 20 nm) and SPIO (size 200 nm) led to enhancement in the entire hemisphere.…”

Section: Leukocyte Labelingmentioning

confidence: 99%

Imaging Neuroinflammation – from Bench to Bedside

Chen¹

2014

J Clin Cell Immunol

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Neuroinflammation plays a central role in a variety of neurological diseases, including stroke, multiple sclerosis, Alzheimer’s disease, and malignant CNS neoplasms, among many other. Different cell types and molecular mediators participate in a cascade of events in the brain that is ultimately aimed at control, regeneration and repair, but leads to damage of brain tissue under pathological conditions. Non-invasive molecular imaging of key players in the inflammation cascade holds promise for identification and quantification of the disease process before it is too late for effective therapeutic intervention. In this review, we focus on molecular imaging techniques that target inflammatory cells and molecules that are of interest in neuroinflammation, especially those with high translational potential. Over the past decade, a plethora of molecular imaging agents have been developed and tested in animal models of (neuro)inflammation, and a few have been translated from bench to bedside. The most promising imaging techniques to visualize neuroinflammation include MRI, positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical imaging methods. These techniques enable us to image adhesion molecules to visualize endothelial cell activation, assess leukocyte functions such as oxidative stress, granule release, and phagocytosis, and label a variety of inflammatory cells for cell tracking experiments. In addition, several cell types and their activation can be specifically targeted in vivo, and consequences of neuroinflammation such as neuronal death and demyelination can be quantified. As we continue to make progress in utilizing molecular imaging technology to study and understand neuroinflammation, increasing efforts and investment should be made to bring more of these novel imaging agents from the “bench to bedside.”

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Passage of DMP Across a Disrupted BBB in the Context of Antibody-mediated MR Imaging of Brain Metastases

Cited by 5 publications

References 3 publications

MRI‐based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE

MRI‐based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE

Efficient and Rapid Labeling of Transplanted Cell Populations with Superparamagnetic Iron Oxide Nanoparticles Using Cell Surface Chemical Biotinylation for in Vivo Monitoring by MRI

Imaging Neuroinflammation – from Bench to Bedside

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