Mass Spectrometry Imaging in Drug Development

Nilsson, Anna; Goodwin, Richard J. A.; Shariatgorji, Mohammadreza; Vallianatou, Theodosia; Webborn, Peter J. H.; Andrén, Per E.

doi:10.1021/ac504734s

Cited by 164 publications

(132 citation statements)

References 136 publications

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“…However this method provides a measure of total drug concentrations that does not give a picture of the heterogeneity of drug distribution in tissues, related to the structural complexity of the neoplastic tissue and the influence of tumor microenvironment that markedly affect drug penetration2. Therefore methods are needed to show the drug’s spatial distribution in the tumor tissue3. The penetration of a drug in tumor depends first on its physicochemical characteristics, but the abnormal vasculature, reactive stroma, and inflammation that characterize tumor microenvironment are all important4.…”

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confidence: 99%

Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging

Giordano

Zucchetti

Decio

et al. 2016

Sci Rep

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The penetration of anticancer drugs in solid tumors is important to ensure the therapeutic effect, so methods are needed to understand drug distribution in different parts of the tumor. Mass spectrometry imaging (MSI) has great potential in this field to visualize drug distribution in organs and tumor tissues with good spatial resolution and superior specificity. We present an accurate and reproducible imaging method to investigate the variation of drug distribution in different parts of solid tumors. The method was applied to study the distribution of paclitaxel in three ovarian cancer models with different histopathological characteristics and in colon cancer (HCT116), breast cancer (MDA-MB-231) and malignant pleural mesothelioma (MPM487). The heterogeneous drug penetration in the tumors is evident from the MALDI imaging results and from the images analysis. The differences between the various models do not always relate to significant changes in drug content in tumor homogenate examined by classical HPLC analysis. The specificity of the method clarifies the heterogeneity of the drug distribution that is analyzed from a quantitative point of view too, highlighting how marked are the variations of paclitaxel amounts in different part of solid tumors.

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Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging

Giordano

Zucchetti

Decio

et al. 2016

Sci Rep

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“…MALDI imaging mass spectrometry (IMS) is a popular alternative to ICP-MS. MALDI IMS analysis visualizes multiple mass to charge ( m/z) ratios of molecules of interest simultaneously, and has been widely used for proteins, peptides, lipids, drugs and metabolites13. In a previous study, MALDI IMS was used to map the distribution of oxaliplatin and its metabolites in rat kidneys10.…”

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confidence: 99%

Chemical Imaging of Platinum-Based Drugs and their Metabolites

Liu

Hummon

2016

Sci Rep

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Platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) are widely used therapeutic agents for cancer treatment. Even though the platinum (Pt)-drugs are routinely used clinically, a clear picture of their distribution within tumor tissues is lacking. The current methods to image the distribution of Pt drugs are limited and do not enable the discrimination of the drug from its metabolites. In this manuscript, we demonstrate a methodology that enables chemical imaging of a Pt drug and its metabolites simultaneously and specifically. Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging (MSI) is combined with an on-tissue chemical derivatization using diethyldithiocarbamate (DDTC). DDTC abstracts the Pt atom to generate ionizable complexes that can be imaged by MALDI MSI. We demonstrate that Pt drugs and their metabolites can be specifically imaged. This approach was successfully applied to map the penetration and metabolism of oxaliplatin in hyperthermic intraperitoneal chemotherapy (HIPEC)-like treated 3D colorectal tumor mimics. The distribution of cisplatin and carboplatin was mapped in additional 3D tumor mimics. We demonstrate that the approach can also be used to image the distribution of copper ions in cells. This method has the potential to be used to evaluate the penetration and distribution of a wide range of compounds.

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“…The resulting data may be visualized using a variety of software [2] to depict the localization and abundance of each molecule. MSI has been routinely applied to the study of plants [3], proteins [4], lipids [5], and drug distributions [6]. A common goal of nearly all applications is to achieve high spatial resolution without a loss in analyte detectability.…”

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confidence: 99%

IR-MALDESI Mass Spectrometry Imaging at 50 Micron Spatial Resolution

Bokhart

Manni²,

Garrard

et al. 2017

J. Am. Soc. Mass Spectrom.

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High spatial resolution in mass spectrometry imaging (MSI) is crucial to understanding the biology dictated by molecular distributions in complex tissue systems. Here, we present MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) at 50 μm resolution. An adjustable iris, beam expander, and aspherical focusing lens were used to reduce tissue ablation diameters for MSI at high resolution. The laser beam caustic was modeled using laser ablation paper to calculate relevant laser beam characteristics. The minimum laser spot diameter on the tissue was determined using tissue staining and microscopy. Finally, the newly constructed optical system was used to image hen ovarian tissue with and without oversampling, detailing tissue features at 50 μm resolution.

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Mass Spectrometry Imaging in Drug Development

Cited by 164 publications

References 136 publications

Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging

Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging

Chemical Imaging of Platinum-Based Drugs and their Metabolites

IR-MALDESI Mass Spectrometry Imaging at 50 Micron Spatial Resolution

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