Chemie und Prozesstechnik
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- Alzheimer’s disease (1)
- Amyloid-beta (1)
- Brain (1)
- Copper (1)
- Gadolinium-based contrast agents (GBCAs) (1)
- Iron (1)
- Isotopic analysis (1)
- Laser ablation inductively coupled plasma–mass spectrometry imaging (LA-ICP-MSI) (1)
- Matrix-assisted laser desorption ionization–mass spectrometry imaging (MALDI-MSI) (1)
- Multi-collector inductively coupled plasma-mass spectrometry (ICP-MS) (1)
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Complementarity of molecular and elemental mass spectrometric imaging of Gadovist™ in mouse tissues
(2019)
Drug biodistribution analyses can be considered a key issue in pharmaceutical discovery and development. Here, mass spectrometric imaging can be employed as a powerful tool to investigate distributions of drug compounds in biologically and medically relevant tissue sections. Both matrix-assisted laser desorption ionization–mass spectrometric imaging as molecular method and laser ablation inductively coupled plasma–mass spectrometric imaging as elemental detection method were applied to determine drug distributions in tissue thin sections. Several mouse organs including the heart, kidney, liver, and brain were analyzed with regard to distribution of Gadovist™, a gadolinium-based contrast agent already approved for clinical investigation. This work demonstrated the successful detection and localization of Gadovist™ in several organs. Furthermore, the results gave evidence that gadolinium-based contrast agents in general can be well analyzed by mass spectrometric imaging methods. In conclusion, the combined application of molecular and elemental mass spectrometry could complement each other and thus confirm analytical results or provide additional information.
Alzheimer’s disease (AD) is characterized by accumulation of tau and amyloid-beta in the brain, and recent evidence suggests a correlation between associated protein aggregates and trace elements, such as copper, iron and zinc. In AD, distorted brain redox homeostasis and complexation by amyloid-beta and hyperphosphorylated tau May alter the isotopic composition of essential mineral elements. Therefore, high-precision isotopic analysis may reveal changes in the homeostasis of these elements. We used inductively coupled plasma-mass spectrometry (ICP-MS)-based techniques to determine the total Cu, Fe and Zn contents in the brain, as well as their isotopic compositions in both mouse brain and serum.
Results for male transgenic tau (Line 66, L66) and amyloid/presenilin (5xFAD) mice were compared to those for the corresponding age- and gendermatched wild-type control mice (WT). Our data show that L66 brains showed significantly higher Fe levels than the corresponding WT. Significantly less Cu, but more Zn was found in 5xFAD brains. We observed significantly lighter isotopic compositions of Fe (enrichment in the lighter isotopes) in the brain, and in serum of L66 mice compared to WT. For 5xFAD mice, Zn exhibited a trend towards a lighter isotopic composition in brain and a heavier isotopic composition in serum compared to WT. Neither mouse model yielded differences in the isotopic composition of Cu. Our findings indicate significant pathology-specific alterations of Fe and Zn brain homeostasis in mouse models of AD. The associated changes in isotopic composition May serve as a marker for proteinopathies Underlying AD and other types of dementia.