Mass Spectrometry Imaging Symposium
Stephen Castellino, Ph.D., GlaxoSmithKline
“MALDI Imaging MS: A View of Biology and Chemistry in Drug Development”
Abstract: Matrix-assisted laser desorption/ionization (MALDI) Imaging Mass Spectrometry (IMS) is an emerging technique which can determine the spatial distribution of a drug and its metabolites in tissue samples without the need for labeling techniques. Furthermore, the spatial distribution of endogenous molecules can be determined from the same experiment. This methodology allows for the correlation of analyte tissue distributions with histology images and thereby integrating chemical structures with biological features. This integrated imaging modality offers the potential to enhance our understanding of pharmacology and pathogenesis mechanisms. Equally important, this new tool can serve as a common platform for engaging pathologist, clinicians, biologists and chemists in addressing a wide range of biological and chemical challenges. This presentation will focus on our efforts to couple MALDI IMS and histology in drug development to gain mechanistic insights into drug correlated toxicities and efficacy.
Jeffrey Spraggins, Ph.D., Vanderbilt University
“Biological Applications of MALDI FTICR Imaging Mass Spectrometry: High Spatial Resolution, Resolving Power, and Sensitivity in One Platform”
Abstract: While imaging MS development has traditionally focused on spatial resolution and throughput, mass resolution and accuracy are becoming important new focal points. Driving factors include the need to identify spatially resolved ions directly from tissue and the difficulties introduced by nominally isobaric species. Low-resolution instrumentation can produce ion images that are in fact merged images of several species that fall under a given peak. Not only can this make ion identification extremely difficult, in many cases biologically relevant information is lost. In this work we demonstrate the capabilities of FTICR MS for imaging applications including high mass and spatial resolution lipid imaging, visualizing peptide modifications in human lens tissue, and imaging proteins associated with immune response to infectious disease. By combining ultra-high resolving power and mass accuracy with high spatial resolution and throughput, these powerful instruments provide critical technological capabilities for molecular imaging.
Nathalie Y.R. Agar, Ph.D., BWH and DFCI, Harvard Medical School
“Mass Spectrometry Imaging for Molecular Pathology and Drug Development”
Abstract: Mass spectrometry provides a new tool for the direct imaging of tissue during neurosurgery, and can also provide significant insight in the development of drugs targeting tumors of the central nervous system.
Using desorption electrospray ionization mass spectrometry (DESI MS), we rapidly detect tumor metabolites from tissue sections of surgically-resected gliomas without complex or time-consuming preparation. The method was validated by correlating 2D mass spectrometry imaging of glioma specimens with histopathology, and used to detect tumor tissue within seconds to minutes. Imaging tissue sections with DESI MS shows that diagnostic molecular signatures overlap with areas of tumor, thereby indicating tumor margins. We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite at BWH and demonstrate the molecular analysis of surgical tissue during brain surgery.
Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in brain tumors. Using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) in pre-clinical animal models, we visualize drug and metabolites penetration in brain tissue without molecular labeling. We validated heme as a simple and robust MALDI MSI marker of the vasculature and go on to provide examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule signal transduction inhibitors in the brain.
Sheerin Shahidi-Latham, Ph.D., Genentech
“Utility of High Resolution Mass Spectrometry in Drug Discovery and Development”
Abstract: This seminar will provide an overview of high resolution mass spectrometric applications in support of drug discovery and development. Examples will include imaging MALDI MS of dosed tissues in support of drug delivery evaluations, highlighting the broadband approach for the simultaneous detection of drug, metabolites, vehicle, and/or endogenous components (e.g. lipids) attainable from a single imaging run. Additionally, examples demonstrating LC-MS approaches towards biomarker discovery will be provided. The seminar will provide a synopsis of the advantages of high-resolution mass spectrometry, as well as, the technical challenges and opportunities in the context of the pharmaceutical industry.
Date: 3/4/14, 9am to 1pm
Time: 3/4/14, 9am to 1pm
Format: Research Program
Contact: Shannon Hurst - 28543 - firstname.lastname@example.org
Mass Spectrometry Imaging Symposium 3-4-14.pdf (PDF, 770 KB)
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