Imaging of a<i>β</i>-peptide distribution in whole-body mice sections by MALDI mass spectrometry

Stoeckli, Markus; Staab, Dieter; Schweitzer, A.; Gardiner, James; Seebàch, Dieter

doi:10.1016/j.jasms.2007.08.005

Cited by 89 publications

(71 citation statements)

References 12 publications

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“…The method described here enables multimodal analysis of intratumoral drug levels, including high spatial resolution and drug metabolism (22,23). Application of MALDI IMS for imaging of pharmaceutical-unlabeled compounds has been of great interest since introduction of the technology (24,25).…”

Section: Discussionmentioning

confidence: 99%

Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer

Grüner

Winkelmann

Feuchtinger

et al. 2016

Molecular Cancer Therapeutics

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Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrixassisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) as a powerful tool to study drug delivery and spatial tissue distribution in PDAC. We utilized an established genetically engineered mouse model of spontaneous PDAC to examine the distribution of the small-molecule inhibitor erlotinib in healthy pancreas and PDAC. MALDI IMS was utilized on sections of single-dose or long-term-treated mice to measure drug tissue distribution. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P ¼ 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate both with the percentage of atypical glands in the cancer (P ¼ 0.021, r s ¼ 0.59) and the level of erlotinib in those atypical glands (P ¼ 0.019, r s ¼ 0.60). The results of this pilot study present MALDI IMS as a reliable technology to study drug delivery and spatial distribution of compounds in a preclinical setting and support drug imagingbased translational approaches. Mol Cancer Ther; 15(5);

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Section: Discussionmentioning

confidence: 99%

Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer

Grüner

Winkelmann

Feuchtinger

et al. 2016

Molecular Cancer Therapeutics

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“…M atrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was introduced in 1997 [1] and has been widely presented as a powerful method for imaging large [2][3][4][5][6][7][8][9][10][11][12][13][14] and small molecules [15][16][17][18][19][20][21][22][23][24] in tissue. The technique has been applied to a diverse range of applications but there has been particular interest in evaluating opportunities in disease state profiling.…”

Section: Introductionmentioning

confidence: 99%

“…IHC, as with other molecular labeling methods, is often limited in its ability to yield information on multiple species in a single section. Mass spectrometry imaging offers simultaneous label free analysis of multiple species in a single experiment, providing significant insights into disease pathogenesis [4,5,7,9,[12][13][14][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Imaging of Phospholipids in Formalin Fixed Rat Brain Sections by Matrix Assisted Laser Desorption/Ionization Mass Spectrometry

Carter

McLeod

Bunch

2011

J. Am. Soc. Mass Spectrom.

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Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a valuable tool for the analysis of molecules directly from tissue. Imaging of phospholipids is gaining widespread interest, particularly as these lipids have been implicated in a variety of pathologic processes. Formalin fixation (FF) is the standard protocol used in histology laboratories worldwide to preserve tissue for analysis, in order to aid in the diagnosis and prognosis of diseases. This study assesses MALDI imaging of phospholipids directly in formalin fixed tissue, with a view to future analysis of archival tissue. This investigation proves the viability of MALDI-MSI for studying the distribution of lipids directly in formalin fixed tissue, without any pretreatment protocols. High quality molecular images for several phosphatidylcholine (PC) and sphingomyelin (SM) species are presented. Images correspond well with previously published data for the analysis of lipids directly from freshly prepared tissue. Different ionization pathways are observed when analyzing fixed tissue compared with fresh, and this change was found to be associated with formalin buffers employed in fixation protocols. The ability to analyze lipids directly from formalin fixed tissue opens up new doors in the investigation of disease profiles. Pathologic specimens taken for histologic investigation can be analyzed by MALDI-MS to provide greater information on the involvement of lipids in diseased tissue.

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“…Imaging MS has also been extensively used to study the development, functioning, and aging of different organs such as the kidney, prostate, epididymis, and eye lens (65)(66)(67)(68)(69)(70). Beyond the study of isolated tissues or organs, whole-body sections from several model animals such as leeches, mice, and rats have been investigated (71)(72)(73)(74). For these analyses, specialized instrumentation and protocols are necessary for tissue sectioning and handling (72,73).…”

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confidence: 99%

From Whole-body Sections Down to Cellular Level, Multiscale Imaging of Phospholipids by MALDI Mass Spectrometry

Chaurand¹,

Cornett²,

Angel

et al. 2011

Molecular & Cellular Proteomics

119

137

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Significant progress in instrumentation and sample preparation approaches have recently expanded the potential of MALDI imaging mass spectrometry to the analysis of phospholipids and other endogenous metabolites naturally occurring in tissue specimens. Here we explore some of the requirements necessary for the successful analysis and imaging of phospholipids from thin tissue sections of various dimensions by MALDI time-of-flight mass spectrometry. We address methodology issues relative to the imaging of whole-body sections such as those cut from model laboratory animals, sections of intermediate dimensions typically prepared from individual organs, as well as the requirements for imaging areas of interests from these sections at a cellular scale spatial resolution. We also review existing limitations of MALDI imaging MS technology relative to compound identification. Finally, we conclude with a perspective on important issues relative to data exploitation and management that need to be solved to maximize biological understanding of the tissue specimen investigated. Molecular & Cellular Proteomics 10: 10.1074/mcp.O110.004259, 1-11, 2011.Since its introduction in the late 90s (1), MALDI imaging mass spectrometry (MS) technology has witnessed a phenomenal expansion. Initially introduced for the mapping of intact proteins from fresh frozen tissue sections (2), imaging MS is now routinely applied to a wide range of different compounds including peptides, proteins, lipids, metabolites, and xenobiotics (3-7). Numerous compound-specific sample preparation protocols and analytical strategies have been developed. These include tissue sectioning and handling (8 -14), automated matrix deposition approaches and data acquisition strategies (15-21), and the emergence of in situ tissue chemistries (22)(23)(24)(25). Originally performed on sections cut from fresh frozen tissue specimens, methodologies incorporating an in situ enzymatic digestion step prior to matrix application have been optimized to access the proteome locked in formalin-fixed paraffin-embedded tissue biopsies (25)(26)(27)(28)(29). The possibility to use tissues preserved using non-cross-linking approaches has also been demonstrated (30 -32). These methodologies are of high importance for the study of numerous diseases because they potentially allow the retrospective analysis for biomarker validation and discovery of the millions of tissue biopsies currently stored worldwide in tissue banks and repositories.In the past decade, instrumentation for imaging MS has also greatly evolved. Whereas the first MS images were collected with time-of-flight instruments (TOF) capable of repetition rates of a few hertz, modern systems are today capable of acquiring data in the kilohertz range and above with improved sensitivity, mass resolving power, and accuracy, significantly reducing acquisition time and improving image quality (33, 34). Beyond time-of-flight analyzers, other MALDIbased instruments have been used such as ion traps (35-37), Qq TOF instruments (38 -40), and ...

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Imaging of aβ-peptide distribution in whole-body mice sections by MALDI mass spectrometry

Cited by 89 publications

References 12 publications

Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer

Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer

Imaging of Phospholipids in Formalin Fixed Rat Brain Sections by Matrix Assisted Laser Desorption/Ionization Mass Spectrometry

From Whole-body Sections Down to Cellular Level, Multiscale Imaging of Phospholipids by MALDI Mass Spectrometry

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