AL
of endogenous metabolites present in tissue.” He adds, “Combine this with the lower cost of label-free imaging and the ability to correlate the hundreds of molecular changes with histo- pathology and one can easily see how this can benefit pharmaceutical companies.”
In addition, IMS has the potential to reveal molecular markers that may be predictive of adverse events in early stages of drug de- velopment and may help scientists better understand the biological origin of an event. “The economic advantages to earlier termina- tion of a test article within the development pipeline can be enormous,” Cornett says.
A group of German scientists agrees that IMS offers significant benefits, and they wrote: “Since MALDI IMS enables the assessment of spatial molecular arrangements in tissue sections, it goes far beyond microscopy in providing hundreds of different molecular images from a single scan without the need of target-specific reagents. Thus, this technology has the potential to uncover new markers for diagnostic purposes or markers that correlate with disease severity as well as prognosis and therapeutic response.”2
Some scientists already use IMS in advanced forms of therapy, such as immunotherapy. Yasuhiro Matsumura of Japan’s National Can- cer Center and his colleagues used IMS to track the distribution of antibody-drug conjugates (ADCs) in tumors, and concluded that IMS
“is a useful tool to assess ADCs and facilitate the optimization of ADC design.”3
The clinical applications go beyond develop- ing drugs. Richard Zare of Stanford University (Calif.) and his colleagues used desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) plus a statistical technique called LASSO (least absolute shrinkage and selection operator) to “diagnose pancreatic tissue sections and prospectively evaluate sur- gical resection margins from pancreatic cancer surgery,” and reported that the results “pro- vide evidence that the molecular information obtained by DESI-MSI/LASSO from pancreatic tissue samples has the potential to transform the evaluation of surgical specimens.”4
Commercial creations
Scientists interested in using IMS have various options from which to choose. The iMScope TRIO imaging mass microscope from Shimadzu (Columbia, Md.) comes with software that provides a variety of analytical approaches, including principal components analysis and hierarchical cluster analysis.
Scientists can also visit the MS Imaging web- site (
http://ms-imaging.org/wp/) to download BioMap, IMS analysis software developed by Novartis (Basel, Switzerland).
Bruker offers complete IMS systems designed to address specific applications. “Our rapifleX
MALDI TOF/TOF [time-of-flight] system was designed specifically for the high sample throughput and high image resolution neces- sary for statistics-based discovery workflows,” Cornett says. “Bruker’s solariX XR and the newer 2XR systems are ideal platforms for imaging of therapeutics and are already deployed at many of the top 25 pharmaceutical companies.”
The best platform to use depends on the ap- plication. “The required technical features of an IMS platform will vary depending on the biological question,” Gutierrez explains. “While it is desirable for factors such as spatial resolution, mass resolution and mass accu- racy to be high, there are trade-offs that come with increasing these parameters, such as the loss of sensitivity, long acquisition times and large data file sizes—for example, hundreds of gigabytes.”
Those gigabytes of information change what a scientist can see on a slide. The view changes to collections of compounds, reveal- ing a deeper look at what makes biological things work.
References
1. Shimuzu, Y.; Satou, M. et al. Matrix-assisted laser desorption/ionization imaging mass spectrometry reveals changes of phospho- lipid distribution in induced pluripotent stem cell colony differentiation. Anal. Bio- anal. Chem. 2016; doi: 10.1007/s00216-016- 0015-x.
2. Schwamborn, K.; Kriegsmann. M. et al. MALDI imaging mass spectrometry—from
bench to bedside. Biochim. Biophys. Acta 2016; doi: 10.1016/
j.bbapap.2016.10.014.
3. Fujiwara, Y.; Furuta, M. et al. Imaging mass spectrometry for the precise design of
antibody-drug conjugates. Scientific Reports 2016; doi:10.1038/srep24954.
4. Eberlin, L.S.; Margulis, K. et al. Pancreatic cancer surgical resection margins: molec- ular assessment by mass spectrometry imaging. PLoS 2016; doi: 10.1371/journal. pmed.1002108.
MALDI imaging can explore samples, such as this rat brain, in various ways to give scientists more information about the components in a structure. (Image courtesy of Bruker Daltonics.)
AMERICAN LABORATORY 45 JANUARY/FEBRUARY 2017
Mike May is a freelance writer and editor living in Florida. He can be reached at mikemay1959@
gmail.com.
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68