A View on Imaging in Drug Research and Development for Respiratory Diseases

Echteld, C.J.A. van; Beckmann, Nicolau

doi:10.1124/jpet.110.172635

Cited by 15 publications

(10 citation statements)

References 138 publications

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“…The technique has been used to examine bleomycin‐induced lung injury in mice (42, 43). Interestingly, the responses detected in the lungs using micro‐CT were qualitatively similar to those reported here, and both techniques showed images of similar quality (44). A considerable limitation of the micro‐CT studies is the use of radiation doses that are even higher than those adopted in clinical medicine.…”

Section: Discussionsupporting

confidence: 79%

Bleomycin‐induced lung injury in mice investigated by MRI: Model assessment for target analysis

Babin

Cannet

Gérard

et al. 2011

Magnetic Resonance in Med

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Magnetic resonance imaging (MRI) has been used to follow the course of bleomycin-induced lung injury in mice and to investigate two knockout mouse lines with the aim of providing potential therapeutic targets. Bleomycin (0.25 mg/kg) was administered intranasally six times, once a day. MRI was carried out on spontaneously breathing animals up to day 70 after bleomycin. Neither cardiac nor respiratory gating was applied during image acquisition. A long lasting response following bleomycin has been detected by MRI in the lungs of male C57BL/6 mice. Histology showed that, from day 14-70 after bleomycin, fibrosis was the predominant component of the injury. Female C57BL/6 mice displayed a smaller response than males. Bleomycin-induced injury was significantly more pronounced in C57BL/6 than in Balb/C mice. MRI and histology demonstrated a protection against bleomycin insult in female heterozygous and male homozygous cancer Osaka thyroid kinase knockout animals. In contrast, no protection was seen in cadherin-11 knockout animals. In summary, MRI can quantify, in spontaneously breathing mice, bleomycin-induced lung injury. With the ability for repetitive measurements in the same animal, the technique is attractive for in vivo target analysis and compound profiling in this murine model. Magn Reson Med 67:499-509,

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Section: Discussionsupporting

confidence: 79%

Bleomycin‐induced lung injury in mice investigated by MRI: Model assessment for target analysis

Babin

Cannet

Gérard

et al. 2011

Magnetic Resonance in Med

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“…A three-dimensional (3D) ultrashort echo time (UTE) sequence (49,50,56,60) with the following parameters was used for acquisitions on rats and mice (whenever different, parameters for mice are provided in parentheses): repetition time (TR) 2.7 ms, echo time 0.02 ms, flip angle of the excitation pulse 2°(3°), 51360 (77086) projections, field-of-view (FOV) 50 ϫ 50 ϫ 70 (30 ϫ 30 ϫ 50) mm 3 , matrix 128 ϫ 128 ϫ 128 (192 ϫ 192 ϫ 192), 5 (2) averages. The acquisition times for the 3D acquisitions were of 11.6 and 6.9 min for rats and mice, respectively.…”

Section: Methodsmentioning

confidence: 99%

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Egger

Gérard

Vidotto

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230. Am J Physiol Lung Cell Mol Physiol 306: L1064 -L1077, 2014. First published April 11, 2014 doi:10.1152/ajplung.00027.2014.-Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRIassessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis.

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“…Nanoscale particles and carriers have already demonstrated effective applications in the diagnosis of diseases. In addition, some of these nanocompounds, commonly known as theranostic agents, have also shown efficient results in the therapy of these pathologies . Nanoparticles have been reported to be efficacious in anti‐angiogenesis therapy , immunotherapy , and gene therapy of GBM .…”

Section: Introductionmentioning

confidence: 99%

Orotracheal administration of contrast agents: a new protocol for brain tumor targeting

et al. 2015

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The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge, this is the first time that the advantages of a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs.

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A View on Imaging in Drug Research and Development for Respiratory Diseases

Cited by 15 publications

References 138 publications

Bleomycin‐induced lung injury in mice investigated by MRI: Model assessment for target analysis

Bleomycin‐induced lung injury in mice investigated by MRI: Model assessment for target analysis

Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230

Orotracheal administration of contrast agents: a new protocol for brain tumor targeting

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