Imaging Mass Spectrometry: Fundamentals and Applications to Drug Discovery

ArticleinDrug Discovery Today 10(12):823-37 · July 2005with27 Reads
DOI: 10.1016/S1359-6446(05)03458-6 · Source: PubMed
Imaging mass spectrometry (IMS) encompasses a variety of techniques that enable the chemical imaging of analytes, which range in size from atoms and small molecules to intact proteins, directly from biological tissues. IMS is transforming specific areas in biological research with its unique combination of chemical and spatial information. Innovations in instrumentation and imaging protocols will make this approach invaluable at many stages of the drug discovery process, including pharmacological target screening and evaluating the distribution of drug and drug metabolites in cells and tissues. The fundamentals and unique methodology of IMS are discussed, along with exciting new applications to drug discovery science.
    • "Consequently, an intensity of a spectrum at an m/z-value represents the relative abundance of a compound with this m/z-value. Although MALDI is not a quantitative technique, it is extensively used for semi-quantitative comparisons that rely on the relative abundance of molecules with a spectrum or, after the normalization of spectra, between spectra [58,59]. Surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) was presented in 1993 for the first time [60]. "
    [Show abstract] [Hide abstract] ABSTRACT: Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.
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    • "2.1.1 Imaging Time-of-Flight Mass Spectrometry One technique that impressively combined the technological progress in several disciplines is imaging mass spectrometry (Rubakhin, Jurchen, Monroe, & Sweedler, 2005; McDonnel and Heeren, 2007; Heeren, 2014). As the name of the technology indicates, its goal is not only to acquire a mass spectrum but to include spatial information. "
    [Show abstract] [Hide abstract] ABSTRACT: In order to detect different substances present in a sample, mass spectrometry is an important option that can be used to answer that question. Thus this method is a standard technique in analytical chemistry laboratories. As the name indicates, mass spectrometers are used for obtaining information about the mass of the sample, in general the mass of its molecules. In all the different techniques and variations of mass spectrometry, ions of the sample are accelerated with help of specially tailored electrical fields and then separated by different means in their mass to charge ratio. One very important method of mass separation is the Time-of-Flight technique (TOF-MS). In this chapter, the development of Time-of-Flight mass spectrometers in recent years regarding their instrumental improvements as well as regarding their applications will be described.
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    • "PK analysis to assess ADME of drug-like molecules in either animals or human is mandatory in new drug applications submitted for final approval by the regulatory authorities (Rohner et al., 2005; Rubakhin et al., 2005; Greer et al., 2011). The first publication of MSI to assess tissue distribution of small drug-like molecules was by Troendle (et al., 1999) in which the anti-neoplastic drug paclitaxel was imaged in human ovarian tumour. "
    [Show abstract] [Hide abstract] ABSTRACT: In pharmaceutical research, understanding the biodistribution, accumulation and metabolism of drugs in tissue plays a key role during drug discovery and development. In particular, information regarding pharmacokinetics, pharmacodynamics and transport properties of compounds in tissues is crucial during early screening. Historically, the abundance and distribution of drugs have been assessed by well-established techniques such as quantitative whole body autoradiography (WBA) or tissue homogenisation with liquid chromatography-mass spectrometry (LC/MS) analysis. However, WBA does not distinguish active drug from its metabolites and LC/MS, while highly sensitive, does not report spatial distribution. Mass spectrometry imaging (MSI) can discriminate drug and its metabolites and endogenous compounds, while simultaneously reporting their distribution. MSI data are influencing drug development and currently used in investigational studies in areas such compound toxicity. In in vivo studies MSI results may soon be used to support new drug regulatory applications, though clinical trial MSI data will take longer to be validated for incorporation into submissions. We review the current and future applications of MSI, focussing on applications for drug discovery and development, with examples to highlight the impact of this promising technique in early drug screening. Recent sample preparation and analysis methods that enable effective MSI, including quantitative analysis of drugs from tissue sections will be summarised and key aspects of methodological protocols to increase the effectiveness of MSI analysis for previously undetectable targets addressed. These examples highlight how MSI has become a powerful tool in drug research and development and offers great potential in streamlining the drug discovery process. This article is protected by copyright. All rights reserved.
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