Abstract
A sensitive, simple and reproducible protocol for nanoparticle-assisted laser desorption/ionization mass spectrometry imaging technique is described. The use of commercially available TiO2 nanoparticles abolishes heterogeneous crystallization, matrix background interferences and enhances signal detection, especially in the low mass range. Molecular image normalization was based on internal standard deposition on tissues, allowing direct comparison of drug penetration and distribution between different organs and tissues. The method was applied to analyze the distribution of the anticancer drug paclitaxel, inside normal and neoplastic mouse tissue sections. Spatial resolution was good, with a linear response between different in vivo treatments and molecular imaging intensity using therapeutic drug doses. This technique distinguishes the different intensity of paclitaxel distribution in control organs of mice, such as liver and kidney, in relation to the dose. Animals treated with 30 mg/kg of paclitaxel had half of the concentration of those treated with 60 mg/kg. We investigated the spatial distribution of paclitaxel in human melanoma mouse xenografts, following different dosage schedules and found a more homogeneous drug distribution in tumors of mice given repeated doses (5×8 mg/kg) plus a 60 mg/kg dose than in those assigned only a single 60 mg/kg dose. The protocol can be readily applied to investigate anticancer drug distribution in neoplastic lesions and to develop strategies to optimize and enhance drug penetration through different tumor tissues.
Highlights
Mass spectrometry imaging (MSI) is one of the latest, rapidly growing, innovative techniques in mass spectrometry (MS) [1]
Identification of PTX Residues with MALDI TOF/TOF using TiO2 Nanoparticles In MALDI experiments PTX is observed in positive ion mode as an adduct with Na+ or K+ at m/z 877 and 892 respectively [41,42]
We have demonstrated the feasibility of measuring the distribution of PTX in tissues and tumor using the n-PALDI protocol developed for MSI
Summary
Mass spectrometry imaging (MSI) is one of the latest, rapidly growing, innovative techniques in mass spectrometry (MS) [1]. Images can be obtained from single cells to whole animal sections, from plants, bacteria, animals and human tissues [3,4,5,6,7]. In a typical MSI experiment, a tissue section is deposited on a steel plate, sprayed with a matrix solution and analyzed by matrixassisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF). The distribution of biomolecules on a tissue section can be readily visualized in two-dimensions, assigning to each pixel the ion intensity specific for the molecule under study. As each individual image pixel can be a full mass spectrum, a number of images can be created from a single experiment, just selecting the different mass values available in the spectrum
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have