Application of MALDI Tissue Imaging of Drugs and Metabolites: A New Frontier for Molecular Histology

Shanta, Selina Rahman; Kim, Young‐Jun; Kim, Young‐Hwan; Kim, Kwang Pyo

doi:10.4062/biomolther.2011.19.2.149

Cited by 7 publications

(5 citation statements)

References 32 publications

(33 reference statements)

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“…The most widespread form of MSI used to analyze biological samples is MALDI‐MS . This technique has been widely applied to identify different metabolites in plant or animal including insect tissues …”

Section: Introductionmentioning

confidence: 99%

“…Drying a sample causes its deformation and thus changes its morphology. Additionally, as online laser focus readjustment towards 3‐D shape of the biological sample surface on MALDI‐MS instrument during imaging is by now technically impossible, significant differences in signal intensities are inevitable . In addition to different flows of laser desorbed ions, the differences in thickness from one side of the sample to the other and its roughness may lead to different electric charging and discharging associated with dissipation of photoelectrons formed after the UV‐laser irradiation.…”

Section: Introductionmentioning

confidence: 99%

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Mass spectrometry imaging of surface lipids on intact Drosophila melanogaster flies

et al. 2014

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The spatial distribution of neutral lipids and semiochemicals on the surface of six-day-old separately reared naive Drosophila melanogaster flies has been visualized and studied using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and laser-assisted desorption/ionization (LDI)-TOF imaging (MSI). Metal targets were designed for two-dimensional MSI of the surface of 3-D biological objects. Targets with either simple grooves or profiled holes designed to accurately accommodate the male and female bodies were fabricated. These grooves and especially holes ensured correct height fixation and spatial orientation of the flies on the targets after matrix application and sample drying. For LDI-TOF to be used, the flies were arranged into holes and fixed to a plane of the target using fast-setting glue. In MALDI-TOF mode, the flies were fixed as above and sprayed with a lithium 2,5-dihydroxybenzoate matrix using up to 100 airbrush spray cycles. The scanning electron microscopy images revealed that the deposits of matrix were homogenous and the matrix formed mostly into the clusters of crystals (40-80 µm) that were separated from each other by an uncovered cuticle surface (30-40 µm). The MSI using target with profiled holes provided superior results to the targets with simple grooves, eliminating the ion suppression/mass deviation due to the 3-D shape of the flies. Attention was paid to neutral lipids and other compounds including the male anti-attractant 11-cis-vaccenyl acetate for which the expected distribution with high concentration on the tip of the male abdomen was confirmed. The red and blue mass shift (PlusMinus1 colour scale) was observed associated with mass deviation predominantly between ±0.2 and 0.3 Da. We use in-house developed software for mass recalibration, to eliminate the mass deviation effects and help with the detection of low-intensity mass signals.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mass spectrometry imaging of surface lipids on intact Drosophila melanogaster flies

et al. 2014

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“…New approaches to obtain direct molecular analysis of drugs and metabolites in tissue are maturing and expanding . The most prominent and widely developed imaging approach to date has been matrix assisted laser desorption/ionization (MALDI)‐MS . With the intense investment in MALDI‐based imaging in both the academic and industrial sectors, both the value and limitations of this technology have quickly become apparent .…”

Section: Introductionmentioning

confidence: 99%

“…New approaches to obtain direct molecular analysis of drugs and metabolites in tissue are maturing and expanding. [2,[13][14][15] The most prominent and widely developed imaging approach to date has been matrix assisted laser desorption/ionization (MALDI)-MS. [16][17][18][19][20][21] With the intense investment in MALDI-based imaging in both the academic and industrial sectors, both the value and limitations of this technology have quickly become apparent. [2,22] With MALDI-based imaging, there remains a need for tissue preparation prior to analysis including, but not always limited to, a chemical matrix application and, typically, a need to carry out the analysis in the vacuum chamber of the mass spectrometer.…”

Section: Introductionmentioning

confidence: 99%

Analysis of chloroquine and metabolites directly from whole‐body animal tissue sections by liquid extraction surface analysis (LESA) and tandem mass spectrometry

et al. 2012

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The rapid and direct analysis of the amount and spatial distribution of exogenous chloroquine (CHQ) and CHQ metabolites from tissue sections by liquid extraction surface sampling analysis coupled with tandem mass spectrometry (LESA-MS/MS) was demonstrated. LESA-MS/MS results compared well with previously published CHQ quantification data collected by organ excision, extraction and fluorescent detection. The ability to directly sample and analyze spatially resolved exogenous molecules from tissue sections with minimal sample preparation and analytical method development has the potential to facilitate the assessment of target tissue penetration of pharmaceutical compounds, to establish pharmacokinetic/pharmacodynamic relationships, and to complement established pharmacokinetic methods used in the drug discovery process during tissue distribution assessment.

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“…The high lateral spatial resolution and utility SIMS can provide is seen in Scheme 3 (III). If such high spatial resolution is not required, MALDI MSI is a versatile alternative that has been employed for imaging drugs and metabolites [39], lipids [40], peptides [41], and proteins [42]. In MALDI MSI, the tissue is coated with a thin layer of matrix and irradiated with a laser beam.…”

Section: Mass Spectrometry Imaging Fundamentalsmentioning

confidence: 99%

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites

Lietz

Gemperline

2013

Advanced Drug Delivery Reviews

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Mass spectrometric imaging (MSI) has rapidly increased its presence in the pharmaceutical sciences. While quantitative whole-body autoradiography and microautoradiography are the traditional techniques for molecular imaging of drug delivery and metabolism, MSI provides advantageous specificity that can distinguish the parent drug from metabolites and modified endogenous molecules. This review begins with the fundamentals of MSI sample preparation/ionization, and then moves on to both qualitative and quantitative applications with special emphasis on drug discovery and delivery. Cutting-edge investigations on sub-cellular imaging and endogenous signaling peptides are also highlighted, followed by perspectives on emerging technology and the path for MSI to become a routine analysis technique.

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Application of MALDI Tissue Imaging of Drugs and Metabolites: A New Frontier for Molecular Histology

Cited by 7 publications

References 32 publications

Mass spectrometry imaging of surface lipids on intact Drosophila melanogaster flies

Mass spectrometry imaging of surface lipids on intact Drosophila melanogaster flies

Analysis of chloroquine and metabolites directly from whole‐body animal tissue sections by liquid extraction surface analysis (LESA) and tandem mass spectrometry

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites

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