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Mass Spectrometry Imaging of the Hypoxia Marker Pimonidazole in a Breast Tumor Model

Title data

Mascini, Nadine E. ; Cheng, Menglin ; Jiang, Lu ; Rizwan, Asif ; Podmore, Helen ; Bhandari, Dhaka R. ; Römpp, Andreas ; Glunde, Kristine ; Heeren, Ron M. A.:
Mass Spectrometry Imaging of the Hypoxia Marker Pimonidazole in a Breast Tumor Model.
In: Analytical Chemistry. Vol. 88 (2016) Issue 6 . - pp. 3107-3114.
ISSN 1520-6882
DOI: https://doi.org/10.1021/acs.analchem.5b04032

Abstract in another language

Although tumor hypoxia is associated with tumor aggressiveness and resistance to cancer treatment, many details of hypoxia-induced changes in tumors remain to be elucidated. Mass spectrometry imaging (MSI) is a technique that is well suited to study the biomolecular composition of specific tissue regions, such as hypoxic tumor regions. Here, we investigate the use of pimonidazole as an exogenous hypoxia marker for matrix-assisted laser desorption/ionization (MALDI) MSI. In hypoxic cells, pimonidazole is reduced and forms reactive products that bind to thiol groups in proteins, peptides, and amino acids. We show that a reductively activated pimonidazole metabolite can be imaged by MALDI-MSI in a breast tumor xenograft model. Immunohistochemical detection of pimonidazole adducts on adjacent tissue sections confirmed that this metabolite is localized to hypoxic tissue regions. We used this metabolite to image hypoxic tissue regions and their associated lipid and small molecule distributions with MALDI-MSI. We identified a heterogeneous distribution of 1-methylnicotinamide and acetylcarnitine, which mostly colocalized with hypoxic tumor regions. As pimonidazole is a widely used immunohistochemical marker of tissue hypoxia, it is likely that the presented direct MALDI-MSI approach is also applicable to other tissues from pimonidazole-injected animals or humans.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Lehrstuhl Bioanalytik und Lebensmittelanalytik > Lehrstuhl Bioanalytik und Lebensmittelanalytik - Univ.-Prof. Dr. Andreas Römpp
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Lehrstuhl Bioanalytik und Lebensmittelanalytik
Result of work at the UBT: No
DDC Subjects: 500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 09 Jul 2018 08:11
Last Modified: 09 Jul 2018 08:11
URI: https://eref.uni-bayreuth.de/id/eprint/44989