Element distribution is altered in a zone surrounding human glioblastoma multiforme.

Recent data indicate that A(1) adenosine receptor (A(1)AR) density is increased in a zone surrounding human and experimental gliomas. On the contrary, tumor tissue and adjacent brain tissue show low to intermediate A(1)AR densities. In order to assess whether changes in A(1)AR expression are indicating further processes of a chemical reorganization of the peritumoral zone, we investigated element concentrations and distribution patterns of copper and zinc in six human glioblastoma multiforme (GBM) specimens by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Uranium and lead were used as external standards. Copper and zinc levels were increased in a peritumoral zone corresponding to the region of elevated A(1)AR density. They showed a lower density in the solid tumor in comparison to surrounding brain tissue, although the cellular density was higher within GBM. Our findings suggest that the immediate vicinity of GBM is characterized by increased levels of copper and zinc supporting the view that higher A(1)AR density surrounding GBM is not an isolated alteration of peritumoral tissue but an indicator of complex changes in the vicinity of infiltrative tumors. Further research is needed to explore the pathophysiological consequences of altered peritumoral element distribution.

Quantifying the A1AR distribution in peritumoural zones around experimental F98 and C6 rat brain tumours.

Quantification of growth in experimental F98 and C6 rat brain tumours was performed on 51 rat brains, 17 of which have been further assessed by 3D tumour reconstruction. Brains were cryosliced and radio-labelled with a ligand of the peripheral type benzodiazepine-receptor (pBR), (3)H-Pk11195 [(1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propylene)-3-isoquinoline-carboxamide)] by receptor autoradiography. Manually segmented and automatically registered tumours have been 3D-reconstructed for volumetric comparison on the basis of (3)H-Pk11195-based tumour recognition. Furthermore automatically computed areas of -300 microm inner (marginal) zone as well as 300 microm and 600 microm outer tumour space were quantified. These three different regions were transferred onto other adjacent slices that had been labelled by receptor autoradiography with the A(1) Adenosine receptor (A(1)AR)-ligand (3)H-CPFPX ((3)H-8-cyclopentyl-3-(3-fluorpropyl)-1-propylxanthine) for quantitative assessment of A(1)AR in the three different tumour zones. Hence, a method is described for quantifying various receptor protein systems in the tumour as well as in the marginal invasive zones around experimentally implanted rat brain tumours and their representation in the tumour microenvironment as well as in 3D space. Furthermore, a tool for automatically reading out radio-labelled rat brain slices from auto radiographic films was developed, reconstructed into a consistent 3D-tumour model and the zones around the tumour were visualized. A(1)AR expression was found to depend upon the tumour volume in C6 animals, but is independent on the time of tumour development. In F98 animals, a significant increase in A(1)AR receptor protein was found in the Peritumoural zone as a function of time of tumour development and tumour volume.