Assessment of the peripheral benzodiazepine receptors in human gliomas by two methods

This study was designed to evaluate the density of peripheral benzodiazepine receptor (PBR) sites as a function of tumor malignancy in human gliomas, and to compare the results obtained with autoradiographic and liquid scintillation measurements performed on the same tissue specimens. In vitro binding of [3H]PK-11195[1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoguinol ine carboxamide] to human gliomas in radioligand binding studies revealed a significantly higher level (about 3 fold) of PBR binding sites in both low grade and high grade gliomas as compared to normal cortex. The Bmax (mean +/- SD) of high and low grade gliomas, when entire tissue sections were measured by autoradiography, was 5.5 +/- 0.3 pmol/mg-tissue (n = 5) and 1.8 +/- 0.9 pmol/mg-tissue (n = 6), respectively, although it was evident that there was area of hot spots in the high grade tumors. This difference was significant (p < 0.05; two-tailed t-test). Similarly, the KD values (dissociation constant; nM) between the high (KD = 20.4 +/- 1.3 nM) and low (KD = 14.3 +/- 2.1 nM) grade gliomas were significantly different. A significant difference in binding site density (Bmax) between the two types of gliomas was also obtained in liquid scintillation measurements. The hot spot areas which showed the most intense binding of [3H]PK-11195 had KD of 24.5 +/- 1.0 nM and Bmax of 6.2 +/- 0.42 pmol/mg-tissue, values significantly higher (p < 0.05, two-tailed t-test) than those obtained when the entire tissue section was measured. The data on the Bmax/KD ratios presented here suggest that it might be possible to differentiate high from low grade gliomas in human by in vivo imaging with 11C-labelled PK-11195.