ro-16-0154 and Mental-Disorders

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

A phase 2 study of 123I-Iomazenil (IMZ) was performed to evaluate its clinical usefulness in SPECT imaging of central-type benzodiazepine receptors (BZR). A total of 246 patients with various central nervous system disorders [82 with epilepsy, 94 with cerebrovascular disease (CVD), 47 with degenerative disorders, 14 with mental disorders relating to BZR and 9 with other diseases] were intravenously injected with 111-222 MBq of IMZ. Early and late images were obtained 15 min and 180 min after injection as the mid-scan time, respectively. In comparison with regional cerebral blood flow (rCBF) images, the uptake of IMZ in the late images, which reflect the regional distribution of BZR, was relatively preserved compared to the uptake of CBF tracers in most of the patients with CVD. In the area of hyperperfusion in the subacute phase of cerebral infarction, however, the defects of IMZ uptake were accompanied by increased uptake of the CBF tracers. On the other hand, late IMZ uptake in most of the patients with the other diseases was decreased more significantly than the uptake of the CBF tracers, suggesting that cortical neuronal damage is more prominent than rCBF in these diseases compared to the vascular perfusional state. No adverse reactions were recognized relating to the IMZ administration. These results suggest that IMZ may provide us with valuable information for assessing pathophysiological state in the brain, which are difficult to achieve with other imaging modalities.

Topics: Adult; Brain Diseases; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Mental Disorders; Middle Aged; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

A phase 2 clinical study of 123I-iomazenil (IMZ) was performed to evaluate its clinical usefulness as central-type benzodiazepine receptor imaging agent in 81 cases with epilepsy, 82 cases with cerebrovascular diseases (CVD), 35 cases with degenerative disorders and 14 cases with mental disorders. In epilepsy, IMZ SPECT images for detection of epileptic foci showed relatively high specificity compared with EEG recording in not only interictal but also ictal state, in spite of the fact that IMZ SPECT images was performed during interictally. It was surmised that IMZ SPECT provides valuable clinical information for detection of epileptic foci which are hard to be diagnosed by EEG. The frequency of abnormal findings by IMZ late images was higher than that by interictal blood flow images and comparable to that by ictal blood flow images. In patients with CVD, different observations were obtained between IMZ late images and blood flow images; for example, in regions of hemodynamic cerebral ischemia, postischemic reperfusion and other pathological perfusion, IMZ late images seemed to reflect the degree of cortical neuronal loss. In patients with degenerative disorders, the binding potential (calculated by a simple quantitative method for IMZ) and other parameters correlated with the dementia score. While the number of examined cases with mental disorders was limited, the frequency of abnormal findings with IMZ imaging was higher than that with morphological imaging.

Topics: Adult; Brain Diseases; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Mental Disorders; Middle Aged; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Brain; Female; Flumazenil; Humans; Iodine Radioisotopes; Mental Disorders; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

The purpose of this study is visual evaluation of the distribution of I-123 iomazenil in the brains of patients with various types of mental disorder and to examine whether chronic administration of a clinical dose of benzodiazepine (BZ) affects the binding of I-123 iomazenil to BZ receptors (BZR). The subjects were 10 patients with mental disorders (3 males and 7 females) with a mean age of 26.8 yrs (range 19-39 yrs). Four of 10 patients were administered BZ for over 3 months and the other six were free of BZ for over one month. The SPECT images were obtained at 5-25 min (early) and 170-190 min (delayed), after the bolus i.v. injection of 167 MBq of I-123 iomazenil, with a triple-head gamma camera. The images were visually evaluated and the washout ratios of each region were calculated. In visual analysis, abnormalities were recognized in 5 patients on the delaye SPECT. The abnormalities were recognized more frequently in the superior frontal lobe. The washout ratio was higher in the BZ (+) patient group than in the BZ (-) patient group. I-123 iomazenil is useful, because the SPECT image with I-123 iomazenil reflects the distribution of BZR on the brain and provides the different information from that obtained with perfusion SPECT, X-ray CT or MRI. The rapid washout of I-123 iomazenil from the brains of BZ (+) patients suggests that chronic administration of a clinical dose of BZ affects the binding of I-123 iomazenil to BZR.

Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Brain; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Mental Disorders; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon