ro-16-0154 and Nervous-System-Diseases

This study examined the usefulness of 123I-iomazenil SPECT (IMZ-SPECT), a type of brain scintigram that focuses on the central benzodiazepine receptor in order to determine its distribution and the function of inhibitory neurons. IMZ-SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Interictal study by IMZ-SPECT is widely available at numerous institutions and its usefulness has been confirmed in patients with not only focal cortical dysplasia and hippocampal sclerosis, but also tuberous sclerosis and neuronal migration disorders, even when magnetic resonance image fails to demonstrate any abnormal findings. When interpreting scintigrams, the developmental dynamic change of the central benzodiazepine receptor in childhood and the duration of the benzodiazepine exposure period should be taken into consideration. It is expected that IMZ-SPECT will be used in various neurological disorders other than epilepsy in the future allow medical services to be provided based on findings in the inhibitory synaptic system obtained with IMZ-SPECT.

Topics: Brain; Epilepsy; Flumazenil; Humans; Iodine Radioisotopes; Nervous System Diseases; Radiopharmaceuticals; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Iomazenil (IMZ) is a partial inverse agonist of central-type benzodiazepine receptors (BZR) which binds specifically to BZR with high affinity. A multi-center Phase 3 clinical study was performed to evaluate the clinical usefulness of 123I-IMZ-SPECT in the diagnosis of brain disorders in 169 patients with degenerative neurological diseases and 37 patients with mental disorders such as neurotic, stress-related and somatoform disorders. In dementia, the decrease in activity in late images, obtained three hours after administration of 123I-IMZ, correlated negatively with the dementia score. In Parkinson's disease and spinocerebellar degeneration. 123I-IMZ showed a more profound decrease in uptake in late images than seen in the cerebral blood flow (CBF) images, and this decrease was in proportion to the duration and severity of the illness. In mental disorders, the ratio of the late to early image counts showed a negative correlation with Hamilton's anxiety scale in all regions in the brain cortices. In panic disorders, the ratio of the cerebral count to the cerebellar count in the late images correlated negatively with the severity of the attack in the frontal, temporal and parietal cortices. These results suggest that 123I-IMZ-SPECT enables us to evaluate the neuronal damage in degenerative diseases and the decrease in the BZR binding potential in mental disorders.

Topics: Adult; Aged; Brain; Female; Flumazenil; GABA-A Receptor Agonists; Humans; Iodine Radioisotopes; Japan; Male; Mental Disorders; Middle Aged; Nerve Degeneration; Nervous System Diseases; Predictive Value of Tests; Tomography, Emission-Computed, Single-Photon