<i>In Vivo</i> mouse imaging and spectroscopy in drug discovery

Beckmann, Nicolau; Kneuer, Rainer; Gremlich, Hans‐Ulrich; Karmouty‐Quintana, Harry; Blé, François Xavier; Müller, Matthias

doi:10.1002/nbm.1153

Cited by 109 publications

(57 citation statements)

References 298 publications

(317 reference statements)

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“…The high level of autofluorescence and visible light absorption associated with in vivo imaging of fluorophores in the green spectrum greatly limits the tissue depth from which a clear fluorescent signal can be obtained. 54,55 However, the development of near-infrared (NIR) probes has allowed the in vivo analysis of fluorescence to become practical. 56 NIR probes reduce the level of background signal by increasing the signal-to-noise ratio and therefore facilitates fluorescent imaging at greater depths.…”

Section: Bioluminescence Imaging (Bli)mentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Engineered bacteria have the unique potential to overcome traditional therapies' limitations by specifically targeting tumors. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally, either external to (non-invasive species) or within tumor cells (pathogens). Pre-clinical and clinical investigations involving bacterial vectors require relevant means of monitoring vector trafficking and levels over time, and development of bacterial-specific real-time imaging modalities are key for successful development of clinical bacterial gene delivery. This review discusses the currently available imaging technologies and the progress to date exploiting these for monitoring of bacterial gene delivery in vivo.Cancer Gene Therapy ( INTRODUCTIONAlthough the potential anti-cancer effects of acquired bacterial infection have been evident for over 120 years and the presence of bacteria in excised tumors has been noted for over 60 years, 1 it is only in more recent times that the tumor-specific growth of bacteria has been considered for therapeutic purposes. While the precise mechanism(s) behind preferential bacterial tumor colonization remain poorly understood, this phenomenon must relate to unique tumor attributes that separate them from healthy tissues. Factors such as the irregular blood supply; local immune suppression; inflammation; and unique nutrient supply (e.g., purines) in tumors have been proposed to play a role. 2 Bacterial entry into the tumor environment is proposed to be facilitated by the leaky vasculature. Cancer cells are characterized by an aberrantly accelerated metabolism and proliferation leading to an imbalance of oxygen supply and consumption which is a major causative factor of tumor hypoxia. 3 The hypoxic nature of solid tumors enhances the growth of anaerobic and facultatively anaerobic bacteria. In addition, these areas with low oxygen and high interstitial pressure are considered to be an immunological sanctuary, where bacterial clearance mechanisms are greatly inhibited. 4 Necrotic regions are also rich in nutrients favoured by bacteria due to tumor cell turnover. However, tumor selective bacterial colonization now appears to be both bacterial species and tumor origin independent, since aerobic bacteria are also capable of colonising tumors, and even small tumors lacking an anaerobic center are colonised. See Figure 1 for proposed mechanisms.Invasive bacteria can internalize and replicate within tumor cells, while non-invasive bacteria grow externally to tumor cells, within the tumor micro-environment. 5 The tumor selective growth of bacteria has made them an attractive vehicle for the delivery of ...

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Section: Bioluminescence Imaging (Bli)mentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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“…For example, in mouse models of Alzheimer's disease (AD), changes in the brain levels of N-acetylaspartate (NAA), and of myo-inositol, can be observed with good sensitivity and precision that enable the effects of treatment to be observed, and this also holds out the promise of translation to patients in the future. 30 Challenges remain for the full utilization of MRS in clinical settings, however, 31 and some experts believe that this is more likely to occur when performed simultaneously with both PET and MRI. While it is possible to perform joint MRI and MRS studies, currently there are no commercial instruments available enabling the performance of PET and MRI/MRS in a single system.…”

Section: In Vivo Mrs and Mrimentioning

confidence: 99%

Drug Discovery and Development: the Role of NMR

Everett

2015

eMagRes

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NMR spectroscopy has been a technology of fundamental importance to drug discovery and development for the past 40-50 years, principally through its use in the structure elucidation of leads, drugs, their synthetic intermediates, and the degradation products and impurities of those drug molecules. In the past 30 years, another major area of application of NMR spectroscopy has been metabolic profiling or metabonomics studies of drug metabolism, drug safety, drug efficacy, and disease, through studies of biological fluids such as urine and plasma, representing a change in application from the chemical to the biological sciences. This trend has continued with significant progress in the application of in vivo MRI and magnetic resonance spectroscopy (MRS) to the study of disease states and their treatment in patients and in animal models. More recently, new applications of NMR spectroscopy have emerged such as hit-finding and hit-to-lead optimization, impacting directly on these early stages of the drug discovery process. Finally, the discovery of completely new areas, led by NMR spectroscopy, such as pharmacometabonomics, holds out the promise of improvements in personalized medicine in the future. This article will briefly cover all of these areas, and more, as a prelude to more detailed treatments in the following articles of this work.

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“…In preclinical studies, mice have been commonly used because of the possibility of using genetically altered animals and the availability of wide ranges of diseased models. 10 The mice, however, may be the most challenging species to be imaged with HP gas MRI because of the small lung size, small tidal volume, and high respiration rate.…”

Section: Small Animal Imaging With Hyperpolarized 129 Xe Magnetic Resmentioning

confidence: 99%