Molecular imaging

Top PDF Molecular imaging:

Development of Targeted Microbubbles for Ultrasound Molecular Imaging of Breast Cancer

Development of Targeted Microbubbles for Ultrasound Molecular Imaging of Breast Cancer

Jennifer.Wischhusen@inserm.fr. Abstract – A subtype of metastatic breast cancer has recently been identified, in which netrin-1 is over- expressed. Netrin-1 binds to dependence receptors inducing survival, while its absence actively triggers apoptosis. An anti-netrin-1 therapy is under develop- ment, which disrupts ligand-receptor interaction and induces apoptosis. To identify potential responders for such a targeted therapy, netrin-1 expression has to be analyzed. Molecular imaging with ultrasound (US) is able to detect the expression of a specific protein when using targeted contrast agents. Thus, we aim to develop an US molecular imaging approach using microbubbles (MB) functionalized with an anti-netrin-1 antibody. Binding was tested on purified netrin-1 protein in static and dynamic conditions. Anti-netrin-1 MB were validated in in-vitro assays and will be further tested in pre-clinical studies using metastatic breast cancer animal models.
En savoir plus

3 En savoir plus

Molecular Imaging in Tissue and Cells by Computer-assisted Innovative Multiomode Mass Spectrometry: COMPUTIS, a new European Project

Molecular Imaging in Tissue and Cells by Computer-assisted Innovative Multiomode Mass Spectrometry: COMPUTIS, a new European Project

Recent developments showed the possibility of extrapolating these techniques to produce actual molecular image of flat samples with a full mass spectrometry at each pixel down to micrometric scales. The project "COMPUTIS" will aim to develop improved technologies for Molecular Imaging Mass Spectrometry (MIMS), enabling innovative approaches in functional genomics, proteomics and metaboloics, as well as for investigation of tissues and cells.

2 En savoir plus

Kinetic analysis of novel mono- and multivalent VHH-fragments and their application for molecular imaging of brain tumors

Kinetic analysis of novel mono- and multivalent VHH-fragments and their application for molecular imaging of brain tumors

tyrosine kinase domain resulting in a ligand-independent receptor (Wikstrand et al., 1998). The appearance of EGFRvIII is associated with poor tumour prognosis (Shinojima et al., 2003). The EGFR and EGFRvIII have been exploited as targets for molecular imaging and therapeutic applications in a variety of human cancers (Laskin and Sandler, 2004). In recent years several IgG antibodies against EGFR, including cetuximab, have proved successful at therapeutic targeting of the EGFR in clinical trials for peripheral tumours such as head and neck cancer and metastatic colorectal cancer (Blick and Scott, 2007). The same antibody is currently undergoing clinical trials for recurrent GBM (Belda-Iniesta et al., 2006); however, it is generally believed that delivery to the brain tumour remains the major obstacle limiting usefulness of antibody treatment for GBM (Stragliotto et al., 1996).
En savoir plus

20 En savoir plus

Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model

Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model

Title: Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model This PhD thesis focuses on the study of a new class of contrast agent for MRI, the magne- tosomes, which are natural iron-oxide vesicles produced by magnetotactic bacteria. Magneto- somes are naturally coated with a lipid bilayer which content is genetically determined. Lately, researchers have unraveled the proteins content of magnetosome membranes, opening the way to produce genetically functionalized magnetosomes. This PhD work aims at investigating a new alternative path using magnetotactic bacteria to tackle the production of high efficiency MR-based molecular imaging probes. The engineering and production of magnetosomes, car- ried out by our collaborators from the LBC, the Laboratoire de Bio´ energ´ etique Cellulaire, are presented and discussed. We firstly characterize wild type magnetosomes as contrast agent for high field MRI, and compare them with chemically produced iron-oxide nanoparticles. Our results confirm that these magnetosomes present very promising contrasting properties in vitro, and therefore they can be used in vivo as efficient blood pool agent, for vasculature imaging of mouse brain after intravenous injection. Afterward, engineered magnetosomes are tested in a molecular imaging study of a U87 mouse model of glioblastoma. Knowing that α ν β 3 integrins
En savoir plus

197 En savoir plus

Application of aptamers for in vivo Molecular Imaging and Theranostics

Application of aptamers for in vivo Molecular Imaging and Theranostics

A number of issues are still largely unresolved. For example, the degradation of these imaging probes in vivo requires further study. This information is missing from almost all published studies while it is mandatory to better interpret the imaging results. For example, there is an increasing use of natural DNA aptamers whereas it is known that DNA degrades rapidly in plasma, which raises questions about the validity of results obtained several hours after injection. Another issue is the potential toxicity of aptamers that is almost never studied. Aptamers are often considered to have low immunogenicity and low toxicity. However oligonucleotides could potentially be recognized by the innate immune system via germline-encoded-pattern-recognition receptors (PRRs) like Toll-like receptors (TLRs) [85]. Accordingly, aptamers immunogenicity should be more studied before further development. Moreover, their fast excretion through renal clearance could also limit the use of aptamers. One of the solutions is to conjugate the aptamer with high molecular weight molecules that can reduce the renal filtration. For instance, the conjugation of the aptamer with polyethylene glycol (PEG) has been widely used [11]. However, such conjugation could affect the affinity of aptamers. Additionally, too few studies have compared the biodistribution of the imaging probe with that of one comprised of a random sequence of the same size and chemistry. Without this important negative control, it is impossible to determine whether the tumor targeting observed in many studies is due to the interaction of the aptamer with its target or improved passive tumor targeting by the so call "enhanced permeability effect". Indeed, new blood vessels formed during tumor growth are usually disorganized and contain wide pores. In addition, tumors exhibit poor lymphatic drainage. Both of these phenomena can promote the diffusion and trapping of molecular imaging probes within the tumor interstitium, without the need to bind to a specific molecular target [86].
En savoir plus

40 En savoir plus

Molecular imaging of the human pulmonary vascular endothelium using an adrenomedullin receptor ligand

Molecular imaging of the human pulmonary vascular endothelium using an adrenomedullin receptor ligand

human albumin. Another limitation is that approximately 350,000 particles of this tracer are injected and block as many pulmonary vessels in the process. This undesirable ‘‘physical’’ blockage of pulmonary circulation in subjects with an already compromised pulmonary circulation represents a current warning on the product monograph. Furthermore, the product may be allergenic in subjects sensitive to albumin and presents supply issues as it is derived from human albumin. Replacement agents that would provide functional assessment of lung perfusion without these caveats are desirable. Molecular imaging agents targeting the pulmonary vascular endothelium have been evaluated for this purpose. 1
En savoir plus

13 En savoir plus

Brain molecular imaging in pharmacoresistant focal epilepsy: Current practice and perspectives

Brain molecular imaging in pharmacoresistant focal epilepsy: Current practice and perspectives

2 Abstract This review aims at synthetizing data available in brain molecular imaging, i.e. Single Photon Emission Computer Tomography (SPECT) but also inter-ictal Fluoro-Deoxy-Glucose Positron Emission Tomography (FDG PET) in focal epilepsies. SPECT imaging is able to measure regional cerebral blood flow and its major originality remains its ictal imaging value. On the other hand, FDG PET, which has higher spatial resolution and lower background activity than SPECT, enables to define glycolytic metabolism in inter-ictal state. Therefore, inter-ictal FDG PET has higher sensitivity than inter-ictal SPECT, especially in temporal lobe epilepsies (TLE). 18 F-FDG PET is thus a necessary step in pre-surgical evaluation in TLE but
En savoir plus

35 En savoir plus

Comparison of T2 and T2 *-weighted MR molecular imaging of a mouse model of glioma

Comparison of T2 and T2 *-weighted MR molecular imaging of a mouse model of glioma

Abstract Background: Standard MRI has been used for high-grade gliomas detection, albeit with limited success as it does not provide sufficient specificity and sensitivity to detect complex tumor structure. Therefore targeted contrast agents based on iron oxide, that shorten mostly T2 relaxation time, have been recently applied. However pulse sequences for molecular imaging in animal models of gliomas have not been yet fully studied. The aim of this study was therefore to compare contrast-to-noise ratio (CNR) and explain its origin using spin-echo (SE), gradient echo (GE), GE with flow compensation (GEFC) as well as susceptibility weighted imaging (SWI) in T2 and T2* contrast-enhanced molecular MRI of glioma. Methods: A mouse model was used. U87MGdEGFRvIII cells (U87MG), derived from a human tumor, were injected intracerebrally. A 9.4 T MRI system was used and MR imaging was performed on the 10 day after the inoculation of the tumor. The CNR was measured prior, 20 min, 2 hrs and 24 hrs post intravenous tail administration of glioma targeted paramagnetic nanoparticles (NPs) using SE, SWI, GE and GEFC pulse sequences.
En savoir plus

9 En savoir plus

en
                                                                    fr

en fr Smart agents for molecular imaging Des agents intelligents pour l’imagerie moléculaire

2 successfully used since the mid-eighties as magnetic resonance imaging contrast agents. Recent research in this field focuses on molecular imaging probes which hold the promise of MRI visualization of different biomarkers and tissue physiological parameters. The design of such smart probes is based in coordination chemistry concepts that use modulation of the molecular structure to produce a specific biomarker-dependent MRI response. Some representative examples of the potential MRI assessment of enzymatic activities, neurotransmitter concentration, or the redox state are shown. Another active field of research involves the replacement of Gd 3+ complexes by chelates of the more biocompatible, biogenic Mn 2+ . Here the main challenge is to create Mn 2+ complexes that combine MRI efficiency, high thermodynamic stability and resistance to in vivo dissociation.
En savoir plus

17 En savoir plus

Multimodal molecular imaging of atherosclerosis: Nanoparticles functionalized with scFv fragments of an anti-αIIbβ3 antibody

Multimodal molecular imaging of atherosclerosis: Nanoparticles functionalized with scFv fragments of an anti-αIIbβ3 antibody

Abstract Due to the wealth of actors involved in the development of atherosclerosis, molecular imaging based on the targeting of specific markers would substantiate the diagnosis of life threatening atheroma plaques. To this end, TEG4 antibody is a promising candidate targeting the activated platelets (integrin αIIbβ3) highly represented within the plaque. In this study, scFv antibody fragments were used to functionalize multimodal imaging nanoparticles. This grafting was performed in a regio selective way to preserve TEG4 activity and the avidity of the nanoparticles was studied with respect to the number of grafted antibodies. Subsequently, taking advantage of the nanoparticle bimodality, both near infrared fluorescence and magnetic resonance imaging of the atheroma plaque were performed in the ApoE −/− mouse model. Here we describe the design of the targeted nanoparticles, and a quantification method for their detection in mice, both ex vivo and in vivo, highlighting their value as a potential diagnosis agent.
En savoir plus

13 En savoir plus

Conception and synthesis of the new cryptophane for the applications in xenon NMR molecular imaging

Conception and synthesis of the new cryptophane for the applications in xenon NMR molecular imaging

In this context, the objective of this thesis is to design new cryptophanes which can be used as molecular platforms for constructing new 129 Xe MRI biosensors usable for in vivo MRI molecular imaging. To meet this demand, two main difficulties should be resolved. First of all, the high symmetry of cryptophanes is proved to be an important drawback to control the reactivity of a particular position with respect to other equivalent sites. The mono- functionalization step is always inevitable and leads to a complex statistical mixture in all kinds of existing synthetic pathways to biosensors. This strategy complicates the purification steps and jeopardizes the production of large quantities of cryptophane derivatives required for the arduous synthesis of bioprobes. For this reason, there is a systematic discussion about cryptophanes symmetry breaking and different attempts were made to synthesize mono- functionalized molecular cages.
En savoir plus

251 En savoir plus

Pre-clinical and clinical evaluation of nuclear tracers for the molecular imaging of vulnerable atherosclerosis: an overview.

Pre-clinical and clinical evaluation of nuclear tracers for the molecular imaging of vulnerable atherosclerosis: an overview.

Atherosclerosis is a chronic inflammatory disease in which oxidized Low Density Lipoproteins (oxLDL) initiate the inflammatory process at sites of endothelial dysfunction [2 4 –6 ] , . Atherosclerotic plaques initially develop excentrically rather than concentrically [7 ] , and non- or moderately obstructive plaques are responsible for the majority of acute coronary events [8 ] . An increased risk of coronary event is therefore not exclusively correlated with the degree of stenosis of any given plaque but also with the probability for a non-occlusive lesion to rupture or erode [3 , 9 ] . Since coronary angiography only provides information about vessel lumen, non-obstructive vulnerable plaques cannot be detected using this technique. Imaging modalities such as intravascular ultrasound or optical coherence tomography are currently being evaluated for vulnerable plaque detection [10 ] . However, the invasive nature of these techniques limits their use to previously identified high-risk patients [11 ] . There is therefore a clinical need for a non-invasive molecular imaging modality allowing the screening of a large population for the detection of vulnerable coronary plaques. However, no such technique is currently available for routine clinical practice [12 ] . Among the various techniques that are currently being evaluated, nuclear imaging is a highly sensitive non-invasive imaging modality [13 ] .
En savoir plus

15 En savoir plus

Ultrasound Molecular Imaging: How to develop clinical products?

Ultrasound Molecular Imaging: How to develop clinical products?

It has been proposed to exploit the specific property of UCA as strict vascular bed marker to be used for molecular imaging when targeting receptors or proteins of interest are expressed at endothelial level. It is well- known that diseases are accompanied by the expression of various markers at tissue and endothelial levels, the latter being the specific target of targeted UCAs. This is particularly the case for inflammation and angiogenesis (tumor angiogenesis and wound healing) in which the luminal surface of endothelial cells within capillaries and vessels express various well-identified receptors such as selectins, Vascular Cell Adhesion Molecule 1 (VCAM-1), integrins and Vascular Endothelial Growth Factor Receptor (VEGFR).
En savoir plus

4 En savoir plus

PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

not be signi ficant due to the fact that in human, [ 18 F]DPA- 714 is also largely eliminated by the hepatic pathway but with high gall bladder accumulation limiting the radioactiv- ity signal in the intestine. In rats, the lack of gall bladder prevents molecular imaging of the upper part of the intestine. Beyond this, we used [ 18 F]DPA-714 to determine the point at which the level of TSPO was at its highest in the TNBS model in order to characterize the dynamic inflammatory processes in this model. This was done by acquiring images at various time points post TNBS induction, illustrating the possibility to repeat image acquisitions and the possibility to follow the evolution of the disease in an individual patient. While the data revealed the time point at which one can observe the highest level of inflammation, one can also observe heterogeneity, post peak, which revealed a large standard deviation. The origin of the heterogeneity is most likely linked to the disease severity. However, a direct correlation between the uptake of [ 18 F]DPA-714 and a clinical score of the disease was not possible in this study due to the limited number of animals used for the dynamic evaluation (n=6). This proof of principle can of course be extrapolated to humans with a protocol dedicated to the evaluation of therapeutic efficiency or disease progression.
En savoir plus

197 En savoir plus

Comparison of T₂ and T₂ *-weighted MR molecular imaging of a mouse model of glioma

Comparison of T₂ and T₂ *-weighted MR molecular imaging of a mouse model of glioma

Abstract Background: Standard MRI has been used for high-grade gliomas detection, albeit with limited success as it does not provide sufficient specificity and sensitivity to detect complex tumor structure. Therefore targeted contrast agents based on iron oxide, that shorten mostly T2 relaxation time, have been recently applied. However pulse sequences for molecular imaging in animal models of gliomas have not been yet fully studied. The aim of this study was therefore to compare contrast-to-noise ratio (CNR) and explain its origin using spin-echo (SE), gradient echo (GE), GE with flow compensation (GEFC) as well as susceptibility weighted imaging (SWI) in T2 and T2* contrast-enhanced molecular MRI of glioma. Methods: A mouse model was used. U87MGdEGFRvIII cells (U87MG), derived from a human tumor, were injected intracerebrally. A 9.4 T MRI system was used and MR imaging was performed on the 10 day after the inoculation of the tumor. The CNR was measured prior, 20 min, 2 hrs and 24 hrs post intravenous tail administration of glioma targeted paramagnetic nanoparticles (NPs) using SE, SWI, GE and GEFC pulse sequences.
En savoir plus

9 En savoir plus

Elemental and molecular imaging of human full thickness skin after exposure to heavy metals

Elemental and molecular imaging of human full thickness skin after exposure to heavy metals

Biopsies of human skin were embedded in a Tissue-Tek OCT (Sakura Finetek USA, Inc.), frozen in liquid nitrogen and stored at -80°C. Sections of 10 µm were cut on a cryostat, placed on Superfrost+, mounted on slides (Dako, Trappes, France) and fixed in acetone at -20°C for 10 min. Then, they were rinsed with phosphate-buffered saline (PBS) and incubated for 30 min with PBS containing BSA 1% at room temperature. After three times washing with PBS, slides were incubated with primary antibodies, overnight at 4°C in a dark humid chamber. After another cycle of washing, they were incubated with the appropriate secondary Alexa Fluor 568 or 488 labeled antibody at 1/200 dilution (Molecular Probes) for 1 h at room temperature. Nuclei were stained with DAPI (300  M, Sigma- Aldrich, St.Louis, MO, USA). Negative controls were realized without primary antibodies (data not shown). After a final rinsing with PBS, the slides were mounted with the Dako fluorescent mounting system and stored at 4°C, protected from light, until analyzing with a SP5 Leica confocal microscope (magnification: 6630). Quantification analysis was performed using the LeicaQWin Software. Quantifications of all the skin markers were standardized to the epidermis surface.
En savoir plus

9 En savoir plus

Contribution of high mass resolution and accuracy of FTMS to molecular imaging

Contribution of high mass resolution and accuracy of FTMS to molecular imaging

2. IDENTIFICATION METHODS IMPLEMENTED IN IMS High molecular weight compounds Shimma,S. et al. Surf. Interface Sci. 2006, 38(12-13), 1712 Groseclose, M.R. et al. J. Mass Spectrom. 2007, 42(2), 254 Chughtai, K. and Heeren, R.M.A. Chem. Rev. 2010, 110(5), 3237

34 En savoir plus

Ultrafast Molecular Imaging by Laser Induced Electron Diffraction

Ultrafast Molecular Imaging by Laser Induced Electron Diffraction

to reveal the geometrical and orbital structure of the par- ent molecule, but it also is amplified by about an order of magnitude as compared to the single-cycle signal. To conclude, we have suggested a simple yet robust method to extract the molecular structure from the photo-electron spectra of a laser-driven linear, symmetric molecule. It is applicable to any sufficiently symmetric molecular system for which the HOMO, or any molecular orbital contributing to the ionization signal, has specific symmetry properties that would allow for a simple inter- pretation of the diffraction patterns. The detailed struc- ture of the diffraction image reflects the symmetry of the molecular orbital from which the recolliding electron em- anates since this symmetry is conserved during the time- evolution of the system under the combined effect of the
En savoir plus

5 En savoir plus

Gd(III) polyaminocarboxylate chelate: realistic manybody molecular dynamics simulations for molecular imaging applications

Gd(III) polyaminocarboxylate chelate: realistic manybody molecular dynamics simulations for molecular imaging applications

Owing to its high spin S of 7/2, the f 7 gadolinium (III) ion is widely used in magnetic resonance imaging (MRI) to enhance image contrast. The imaging is based on 1 H NMR of the aqueous protons in the organism. The existence of the Gd(III) ion in the abnormal tissue enhances the contrast, modifying the nuclear magnetic relaxation times of the water proton in its vicinity. Because aqueous Gd(III) ions are toxic, it is desirable to use organic Gd(III) complexes instead, in order to avoid a possible release of the free ion in the human body. With the aim at developing more efficient contrast agents, a balance between the stability of the complex and its efficiency must be maintained. As already pointed out by Botta, 1
En savoir plus

14 En savoir plus

en
                                                                    fr

en fr Characterization and Molecular Imaging and Atherosclerotic Plaque : Preclinical Studies Caractérisation et imagerie moléculaire de la plaque d'athérome : études pré-cliniques

dans du sang humain a montré des résultats analogues à ceux obtenus par l’étude in vitro réalisée dans le sang de souris, tant en termes de stabilité dans la fraction libre du plasma qu'[r]

275 En savoir plus

Show all 3634 documents...