In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T

Flament, Julien; Geffroy, Françoise; Medina, Christelle; Robic, Caroline; Mayer, Jean-François; Mériaux, Sébastien; Valette, Julien; Robert, Philippe; Port, Marc; Bihan, Denis Le; Lethimonnier, Franck; Boumezbeur, Fawzi

doi:10.1002/mrm.24217

Cited by 44 publications

(32 citation statements)

References 46 publications

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“…In a similar study, Flament et al used liposome-encapsulated paramagnetic contrast agents conjugated with an RGD peptide for targeting of α v β 3 integrin receptors in U-87 MG mouse brain tumors using MRI. 39 The investigators demonstrated high-sensitivity in vivo MRI of angiogenesis in mouse brain tumors which additionally supports the obtained results showing selective uptake of the targeted RLP in both tumor xenografts studied. It should be pointed out that the gadolinium loading was not optimized for this preliminary study; however, interesting in this context is the fact that localization of the tumor with MRI was better as compared with radiolabeled RLP using micro-SPECT/CT imaging.…”

supporting

confidence: 78%

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

Rangger¹,

Helbok²,

Sosabowski³

et al. 2013

IJN

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Background The significant progress in nanotechnology provides a wide spectrum of nanosized material for various applications, including tumor targeting and molecular imaging. The aim of this study was to evaluate multifunctional liposomal nanoparticles for targeting approaches and detection of tumors using different imaging modalities. The concept of dual-targeting was tested in vitro and in vivo using liposomes derivatized with an arginine-glycine-aspartic acid (RGD) peptide binding to α v β 3 integrin receptors and a substance P peptide binding to neurokinin-1 receptors. Methods For liposome preparation, lipids, polyethylene glycol building blocks, DTPA-derivatized lipids for radiolabeling, lipid-based RGD and substance P building blocks and imaging labels were combined in defined molar ratios. Liposomes were characterized by photon correlation spectroscopy and zeta potential measurements, and in vitro binding properties were tested using fluorescence microscopy. Standardized protocols for radiolabeling were developed to perform biodistribution and micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies in nude mice bearing glioblastoma and/or melanoma tumor xenografts. Additionally, an initial magnetic resonance imaging study was performed. Results Liposomes were radiolabeled with high radiochemical yields. Fluorescence microscopy showed specific cellular interactions with RGD-liposomes and substance P-liposomes. Biodistribution and micro-SPECT/CT imaging of 111 In-labeled liposomal nanoparticles revealed low tumor uptake, but in a preliminary magnetic resonance imaging study with a single-targeted RGD-liposome, uptake in the tumor xenografts could be visualized. Conclusion The present study shows the potential of liposomes as multifunctional targeted vehicles for imaging of tumors combining radioactive, fluorescent, and magnetic resonance signaling. Specific in vitro tumor targeting by fluorescence microscopy and radioactivity was achieved. However, biodistribution studies in an animal tumor model revealed only moderate tumor uptake and no additive effect using a dual-targeting approach.

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supporting

confidence: 78%

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

Rangger¹,

Helbok²,

Sosabowski³

et al. 2013

IJN

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“…Two assays were performed following the generation of the microvessel. We modeled cancer angiogenesis using the U87MG cell line, which is known for its considerable angiogenic potential 21,22 as a cancer sprout inducer from the microvessel. We injected an U87MG-fibrin mixture into the upper channel, followed by a fibrin injection into the bridge channel ( Fig.…”

Section: Metastasis Chip Designmentioning

confidence: 99%

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

et al. 2014

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Understanding the mechanism behind cancer metastasis is a major challenge in cancer biology. Several in vitro models have been developed to mimic a cancer microenvironment by engineering cancer-endothelial cell (EC) and cancer-stromal cell interactions. It has been challenging to realistically mimic angiogenesis, intravasation, and extravasation using macro-scale approaches but recent progress in microfluidics technology has begun to yield promising results. We present a metastasis chip that produce microvessels, where EC and stromal cells can be patterned in close proximity to tumor cells. The vessels are formed following a natural morphogenic process and have smooth boundaries with proper cell-cell junctions. The engineered microvessels are perfusable and have well-defined openings toward inlet and outlet channels. The ability to introduce cancer cells into different locations bordering to the microvessel wall allowed generation and maintenance of appropriate spatial gradients of growth factors and attractants. Cancer angiogenesis and its inhibition by anti-vascular endothelial growth factor (bevacizumab) treatment were successfully reproduced in the metastasis chip. Cancer intravasation and its modulation by treatment of tumor necrosis factor-a were also modeled. Compared to other models, the unique design of the metastasis chip that engineers a clear EC-cancer interface allows precise imaging and quantification of angiogenic response as well as tumor cell trans-endothelial migration. The metastasis chip presented here has potential applications in the investigation of fundamental cancer biology as well as in drug screening. V C 2014 AIP Publishing LLC.

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“…Additionally, controlled release (7, 9) in combination with liposome targeting (10-12) can be utilized to reduce unintended side effects of drugs by delivering the drug preferentially to the desired site. Liposomes have recently been used to deliver a high payload of various magnetic resonance agents either encapsulated or incorporated into the liposome membrane for relaxation and sensitivity enhancement (1, 13, 14). …”

Section: Introductionmentioning

confidence: 99%

Characterization of a lanthanide complex encapsulated with MRI contrast agents into liposomes for biosensor imaging of redundant deviation in shifts (BIRDS)

et al. 2014

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Purposely-designed magnetic resonance imaging (MRI) probes encapsulated in liposomes, which alter contrast by their paramagnetic effect on longitudinal (T1) and transverse (T2) relaxation times of tissue water, hold promise for molecular imaging. However a challenge with liposomal MRI probes that are solely dependent on enhancement of water relaxation is lack of specific molecular readouts, especially in strong paramagnetic environments, thereby reducing the potential for monitoring disease treatment (e.g., cancer) beyond the generated MRI contrast. Previously it has been shown that molecular imaging with magnetic resonance is also possible by detecting the signal of non-exchangeable protons emanating from paramagnetic lanthanide complexes themselves (e.g., TmDOTP5−, which is a Tm3+-containing biosensor based on a macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate), DOTP5−) with a method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). Here we show that BIRDS is useful for molecular imaging with probes like TmDOTP5− even when they are encapsulated inside liposomes with ultra-strong T1 and T2 contrast agents (e.g., Magnevist and Molday ION, respectively). We demonstrate that molecular readouts like pH and temperature determined from probes like TmDOTP5− are resilient, because sensitivity of the chemical shifts to the probe’s environment is not compromised by presence of other paramagnetic agents contained within the same nanocarrier milieu. Because high liposomal encapsulation efficiency allows for robust MRI contrast and signal amplification for BIRDS, nanoengineered liposomal probes containing both monomers like TmDOTP5− and paramagnetic contrast agents could allow high spatial resolution imaging of disease diagnosis (with MRI) and status monitoring (with BIRDS).

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In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T

Cited by 44 publications

References 46 publications

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

A microfluidic platform for quantitative analysis of cancer angiogenesis and intravasation

Characterization of a lanthanide complex encapsulated with MRI contrast agents into liposomes for biosensor imaging of redundant deviation in shifts (BIRDS)

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