Imaging of brain tumors using peripheral benzodiazepine receptor ligands.

Peripheral benzodiazepine receptor ligands were utilized to selectively image intracerebrally implanted C6 gliomas, RG-2 gliomas, and Walker 256 metastatic tumors by means of quantitative autoradiography. Intravenous injections of 3H-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or 3H-flunitrazepam in combination with clonazepam revealed high densities of peripheral benzodiazepine binding in glial tumors, with less binding in metastatic tumors. Peripheral binding was displaced by preadministration of excess PK11195. Topographical correlation was excellent between areas of histologically verified tumor and high densities of peripheral benzodiazepine binding. The choroid plexus, ependyma, and pineal gland also showed a moderate level of binding, but there was little binding in other normal brain structures or necrotic tissue. Binding densities were three- to fivefold higher in C6 glial tumors compared to normal cortex. Injection of 3H-flunitrazepam alone, which binds to both central and peripheral receptors, had the advantage of showing normal anatomic structures in addition to a clear definition of tumor topography. The potential value of peripheral benzodiazepine ligands in selectively imaging brain tumors in man with positron emission tomography is discussed.