Česká společnost pro hmotnostní spektrometrii

(5. konference České společnosti pro hmotnostní spektrometrii - FrO-016)
Molecular and elemental bioimaging of human brain tumors

Barbara Crone ^1 *, Sabrina Kröger ¹, Ann-Christin Niehoff ¹, Uwe Karst ¹

1. Institute of Inorganic and Analytical Chemistry, University of Muenster, Germany

Abstrakt

Glioblastoma is the most common malignant brain tumor. The survival rate can be enhanced by surgical resection supported by contrast enhancement using a fluorescent dye. The administration of 5-aminolevulinic acid (5-ALA), a natural precursor of hemoglobin with fluorescent protoporphyrin IX (PPIX) as intermediate, has been established as an important technique. In this study, a molecular and elemental imaging method combining spatially resolved information from MALDI-MS and LA-ICP-MS is developed for the investigation of 5-ALA, PPIX and heme distribution in human brain tumor tissue.
Experimental conditions for MALDI-MS measurements of 5-ALA, PPIX and heme were optimized by dried droplet analysis of the pure substances. To improve signal to noise ratio, MS/MS experiments were used for PPIX and heme detection. MALDI-MS analysis of the tumor tissue were performed in four different modes using a shift in the pixel arrangement. Small mass ranges were selected to obtain the highest sensitivity, the MS analysis of 5-ALA and PPIX/heme was performed with two mass ranges. Moreover, MS/MS imaging of PPIX and heme improved limits of detection and validated MS data. By applying the MALDI-MS and MALDI-MS/MS imaging method to cryosections of human brain tumor, PPIX accumulation in tissue of high tumor grade could be shown.
Elemental bioimaging of Fe, corresponding to heme, was performed by LA-ICP-MS. For quantification, external calibration with homemade matrix-matched standards was used. Matrix-matched standards based on HEC provided low limits of detection (LOD; 1.1 µg/g) and quantification (LOQ; 3.5 µg/g) according to the 3- and 10-σ criterion. Fe accumulations of over 200 µg/g could be found in the tumor tissue correlating well with blood vessel distribution.

* Korespondující autor: barbaracrone@uni-muenster.de