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

This study was designed to evaluate the density of peripheral benzodiazepine receptor (PER) 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 [H-3]PK-11195[1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3- isoguinoline carboxamide] to human gliomas in radioligand binding studies revealed a significantly higher level (about 3 fold) of PER binding sites in both low grade and high grade gliomas as compared to normal cortex. The B-max (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 K-D values (dissociation constant; nM) between the high (K-D = 20.4 +/- 1.3 nM) and low (K-D = 14.3 +/- 2.1 nM) grade gliomas were significantly different. A significant difference in binding site density (B-max) between the two types of gliomas was also obtained in liquid scintillation measurements. The hot spot areas which showed the most intense binding of [H-3]PK-11195 had K-D of 24.5 +/- 1.0 nM and B-max 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 B-max/K-D ratios presented here suggest that it might be possible to differentiate high from low grade gliomas in human by in vivo imaging with C-11-labelled PK-11195.