Genetic Engineering & Biotechnology News

APR15 2017

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Genetic Engineering & Biotechnology News | GENengnews.com | APRIL 15, 2017 | 13 By merging histology with the molecular information from the MALDI mass spectrom- eter, a histology-directed analysis of the tissue is possible. Figure 2 highlights an extract of early work by S. Castellino et al. 2 A small area of a histology section is magnified showing regions of inflammation. An ion map (50 µm spatial resolution), which corresponds to the same zoomed region, indicates the localization of lapatinib metabolite, M10, is only in the re- gions associated with the inflammation. A recent publication by M. Reid Grose- close et al. 3 evaluated the additional informa- tion that MALDI MSI could provide over and above LC-MS in a nephrotoxicity study on the anticancer drug Dabrafenib (DAB) in rats. This work was in support of developing DAB for use in pediatric patients. Previous studies had identified some unexpected, adverse kid- ney effects, including tubular deposits in some juvenile rats. In this study, MALDI MSI was used to determine the distribution of DAB and primary metabolites in the kidney. Subsequent MSI analysis of the tubular deposits revealed them to be calcium phosphate crystals. Many other papers, posters, and presen- tations have highlighted the power of these new combinations. For example, work on Chloroquine in a Long-Evans male rat model by G. Hochart et al. 4 using a MALDI-FTMS system (Bruker SolariX XR, Figure 3), re- ported that: "Combining the strengths of QWBA and MALDI MSI allowed for the sensitive detection of drug related material (QWBA) and the quantitative differentiation of parent and metabolite (MALDI MSI)." Challenges and Opportunities MALDI MSI using FTMS is still a rela- tively young technique. Advances in instru- mentation and sample processing that have occurred over the past five to seven years have shown the value of the technique to the pharmaceutical industry, where it has been included as supplementary data to regula- tory filings. As the industry continues to recognize the value of MALDI MSI to pro- vide additional insight and inform decisions regarding the development of a candidate compound, we are sure to see such data be- come more common in regulatory submis- sions and eventually become required. It is easy to imagine that the combina- tion of MALDI MSI with QWBA and LC- MS will yield deeper understanding about a drug, and its pharmacology, and toxicol- ogy, to deliver tangible benefits as it moves through development to market. References 1. Pharmaco-Imaging in Drug Biologics Development: "Fundamentals and Applications" pg171, Brian R. Moyer, Narayan P.S. Cheruvu, Tom C.-C. Hu, Editors 2. Castellino S, Groseclose MR, Wagner D. MALDI imaging mass spectrometry: bridging biology and chemistry in drug development. Bioanalysis. 2011 Nov; 3(21):2427-41 3. M. Reid Groseclose, Susan B. Laffan, Kendall S. Frazier, Angela Hughes-Earle, Stephen Castellino. Imaging MS in Toxicology: An Investigation of Juve- nile Rat Nephrotoxicity Associated with Dabrafenib Administration. Journal of The American Society for Mass Spectrometry., 2015, 26(6):887 – 898 4. G. Hochart et al, Comparative Approaches between Quantitative-MSI and Quantitative-WBA: Applica- tion to Chloroquine Administration in a Long-Evans Male Rate Model, Presented at ISSX conference, https://issx.confex.com/issx/intl11/webprogram/ Paper35908.html (Accessed March 2017) VIAFLO II VIAFLO II VOYAGER II VOYAGER II ASSIST ASSIST VIAFLO 96 I 384 Electronic hand held pipette Easy 96 and 384 channel pipetting and increased productivity due to a full range of pipetting modes including repeat dispense, serial dilute and customized programs. Interchangeable pipetting heads allow precise pipetting between 0.5 and 1250 µl. MULTIWELL PLATE PIPETTING EASY AND AFFORDABLE www.integra-biosciences.com EVOLVE EVOLVE MULTIWELL PLATE PIPETTING Drug Discovery Tutorial Dale Shannon Cornett, Ph.D. (shannon. cornett@bruker.com), is applications development manager, mass spectrometry, at Bruker Daltonics. Web: www.bruker.com.

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