ro-16-0154 and Epilepsy

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

Epilepsy is one of the most prevalent neurologic disorders and affects approximately 1% of the population. Most complex seizures arise from the temporal lobes and the condition of 20-30% of these patients is refractory to medication. Many can be rendered seizure free with surgery. Epilepsy surgery requires accurate identification of the site and extent of the epileptogenic area responsible for seizures. EEG is accepted as a gold standard, however only 50% of the patients are safely diagnosed. The need for invasive monitoring with possible hemorrhage or infection has been greatly reduced by the introduction of new technologies such as PET, SPECT and MRI in the clinical practice. MRI demonstrate morphologic changes in approximately 80% of patients with epilepsy. However, structural lesions may not always correlate with clinical, EEG and pathologic localization of epileptogenic foci. Seizures are associated with pronounced changes in regional cerebral blood flow. The real power of SPECT lies in the opportunity of ictal examinations, with a sensitivity ranging from 90 to 97%. Interictal PET studies using 18F-FDG measure regional glucose metabolism, have been investigated for their value as non-invasive focus-localizing techniques. These studies have sensitivity ranging from 80 to 85%. The benzodiazepine binding site that are associated with and modulate the activity of GABA receptors have been imaged by SPECT (using 123I-iomazenil) and PET (using 11C-Flumazenil). Combined measurements of benzodiazepine binding sites and perfusion/metabolism provide a more accurate visualization of epileptogenic site than perfusion or metabolism measurements alone. Functional imaging modalities (PET and SPECT) are highly important in the presurgical evaluation of patients with medically refractory complex partial seizures.

Topics: Animals; Brain; Cerebrovascular Circulation; Epilepsy; Flumazenil; Fluorodeoxyglucose F18; GABA Modulators; Humans; Iodine Radioisotopes; Radiopharmaceuticals; Receptors, Cholinergic; Receptors, GABA; Receptors, GABA-A; Receptors, Histamine H1; Receptors, Opioid; Seizures; Sensitivity and Specificity; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Adoption of standard input function (SIF) has been proposed for kinetic analysis of receptor binding potential (BP), instead of invasive frequent arterial samplings. The purpose of this study was to assess the SIF method in quantitative analysis of [123I]iomazenil (IMZ), a central benzodiazepine antagonist, for SPECT. SPECT studies were performed on 10 patients with cerebrovascular disease or Alzheimer disease. Intermittent dynamic SPECT scans were performed from 0 to 201 min after IMZ-injection. BPs calculated from SIFs obtained from normal volunteers (BPs) were compared with those of individual arterial samplings (BPo). Good correlations were shown between BP(o)s and BP(s)s in the 9 subjects, but maximum BP(s)s were four times larger than the corresponding BP(o)s in one case. There were no abnormal laboratory data in this patient, but the relative arterial input count in the late period was higher than the SIF. Simulation studies with modified input functions revealed that height in the late period can produce significant errors in estimated BPs. These results suggested that the simplified method with one-point arterial sampling and SIF can not be applied clinically. One additional arterial sampling in the late period may be useful.

Topics: Adolescent; Adult; Aged; Algorithms; Alzheimer Disease; Brain; Cerebrovascular Disorders; Epilepsy; Female; Flumazenil; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Radioisotope Dilution Technique; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

123I-Iomazenil (123I-IMZ) and 123I-IMP imaging were performed in 8 epileptic patients (EP) in the interictal phase and 6 normal volunteers (NV). On 123I-IMZ delayed imaging, the 8 EP showed abnormally decreased findings. Two EP showed decreased perfusion in the same region on 123I-IMP imaging. 123I-IMZ imaging for the detection of epileptic foci showed relatively high specificity compared with EEG recording. On 123I-IMZ early images, the count ratio of the right lower frontal cortex was lower the cerebellar cortex in EP was lower than that in NV. On 123I-IMZ delayed images, the count ratio of the bilateral occipital and the right upper and lower frontal cortices to the cerebellar cortex in EP was lower than that in NV. On 123I-IMZ delayed images, the count ratio of the right upper frontal cortex to the occipital cortex in EP was lower than that in NV. On 123I-IMZ delayed images, the count ratio of the left lower frontal cortex to the occipital cortex in EP was higher than that in NV. These results pointed to the involvement of the benzodiazepine receptor complex in epilepsy.

Topics: Adult; Amphetamines; Brain; Cerebrovascular Circulation; Epilepsy; Female; Flumazenil; Humans; Iodine Radioisotopes; Iofetamine; Male; Middle Aged; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Firstly, to compare the findings of interictal 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and of single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propylene-amine-oxime (HMPAO) and 123I-iomazenil in localising the epileptogenic cortex in patients who were candidates for epilepsy surgery, but in whom clinical findings, video EEG monitoring (V-EEG), MRI, and neuropsychological evaluations did not give any definite localisation of the seizure onset. Secondly, to assess the ability of these functional methods to help in the decision about the epilepsy surgery.. Eighteen epileptic patients were studied with FDG-PET and iomazenil-SPECT. HMPAO-SPECT was performed in 11 of these 18 patients. Two references for localisation was used--ictal subdural EEG recordings (S-EEG) and the operated region.. Fifteen of 18 patients had localising findings in S-EEG. FDG-PET findings were in accordance with the references in 13 patients and iomazenil-SPECT in nine patients. HMPAO-SPECT visualised the focus less accurately than the two other methods. In three patients S-EEG showed independent bitemporal seizure onset. In these patients FDG-PET showed no lateralisation. However, iomazenil-SPECT showed temporal lobe lateralisation in two of them.. FDG-PET seemed to localise the epileptogenic cortex more accurately than interictal iomazenil-SPECT in patients with complicated focal epilepsy.

Topics: Adolescent; Adult; Atrophy; Cerebral Cortex; Electroencephalography; Epilepsy; Female; Flumazenil; Fluorodeoxyglucose F18; Glucose; Humans; Magnetic Resonance Imaging; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

A Phase 3 clinical trial of 123I-Iomazenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors (BZR), was performed, and the clinical usefulness of IMZ was evaluated in 121 patients with epilepsy (106 cases with partial epilepsy and 15 cases with generalized epilepsy). A regional abnormality in the BZR distribution was detected in late IMZ images in 20 of 24 cases without abnormal MRI and/or X-ray CT findings. Moreover, only 16 of these 20 cases showed abnormal findings in the cerebral blood flow (CBF) images. In partial epilepsy, abnormal regions in late IMZ images agreed or partially agreed with epileptic foci estimated from the clinical symptoms of epileptic seizures, interictal EEG, and MRI and/or X-ray CT findings in 76%, 70% and 96% of the cases detected. These regions also agreed or partially agreed with the estimated epileptic foci in 92% of the cases with foci estimated by combination of those three methods and in 72% of those estimated by ictal EEG. The agreement or partial agreement rates of late IMZ images with each of the other methods were higher than those of CBF images, although the differences were not significant. For surgically-proven epileptic foci without any abnormality in the CBF image, abnormal regions were detected in late IMZ images. These findings suggest that IMZ SPECT is a useful new tool for detecting epileptic foci based on the distribution of BZR in the brain.

Topics: Adult; Brain; Epilepsy; Female; Flumazenil; GABA-A Receptor Agonists; Humans; Iodine Radioisotopes; Japan; Male; Predictive Value of Tests; Tomography, Emission-Computed, Single-Photon

Single photon emission computed tomography (SPECT) is being increasingly used as an adjunctive technique in the localisation of epileptogenic foci prior to surgery. Fourteen patients (five male, nine female; mean age 31 years) with refractory complex partial seizures, all of whom had abnormal 99Tc HM-PAO SPECT scans, were imaged again using the benzodiazepine receptor ligand 123I-iomazenil. Eleven of these patients displayed the same abnormality on both scans. The magnitude of the deficit, however, was slightly greater (P < 0.05) on the iomazenil scan compared with the HM-PAO study. These 11 patients were then randomised into two groups. Group 1 (n = 7) received clobazam 20 mg/day for a minimum of 7 days before a second iomazenil study was performed. Patients in group 2 (n = 4) underwent a second iomazenil scan at the same time interval as those in group 1, but without the additional clobazam. The resultant scans were reported blind to treatment. There were no qualitative or quantitative differences between the first and second iomazenil studies in either group. Patients can be imaged using 123I-iomazenil without withdrawing clobazam therapy. From this preliminary study, there seems little advantage in using iomazenil in place of HM-PAO to delineate the extent of the zone of epileptogenesis. Whether iomazenil SPECT will prove to be more sensitive in identifying the site of the epileptic focus remains to be determined.

Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Benzodiazepinones; Brain; Clobazam; Epilepsy; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Tomography, Emission-Computed, Single-Photon

When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[. Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7-56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent. In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0.. Concordance between interictal

Topics: Adolescent; Adult; Child; Epilepsy; Female; Flumazenil; Fluorodeoxyglucose F18; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Positron-Emission Tomography; Postoperative Complications; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

It has been suggested, on the basis of a previous pilot study conducted in a small number of patients, that MR imaging-based PVE correction in I-123 iomazenil brain SPECT improves the detectability of cortical epileptogenic foci. In the present study, we performed an investigation by using a larger sample size to establish the effectiveness of the PVE correction and to conduct a detailed evaluation based on the histologic classification of lesions.. Seventy-five patients (male/female, 37/38; age, 28 ± 12 years) with intractable epilepsy who had undergone surgical treatment were enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were performed before the operation in all patients. I-123 iomazenil SPECT images with and without MR imaging-based PVE correction were assessed visually and by semiquantitative analysis based on the AI(%) of the SPECT count in the resected lesions.. The sensitivity, specificity, and accuracy of foci detection by visual assessment were significantly higher after PVE correction compared with the values obtained before the correction. The results of the semiquantitative analysis revealed that the asymmetry of the SPECT counts was significantly increased after the PVE correction in the surgically resected lesions in cases of mesial temporal sclerosis, tumor, and malformations of cortical development.. The effectiveness of MR imaging-based PVE correction in I-123 iomazenil brain SPECT in improving the detection of cortical epileptogenic foci with abnormal histologic findings was established by our investigation conducted on a large sample size.

Topics: Adult; Algorithms; Artifacts; Brain; Epilepsy; False Negative Reactions; Female; Flumazenil; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Radiopharmaceuticals; Reproducibility of Results; Sample Size; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

We present 2 cases of malformations of cortical development and early onset epilepsy. The first case is of a patient with left hemimegalencephaly who developed focal epilepsy at the age of 2 days and cluster spasms at 1.5 months. After left functional hemispherectomy, seizures originated from the contralateral hemisphere, which had shown normal signals in the preoperative magnetic resonance imaging study. The second case is of a patient with lissencephaly, caused by a missense mutation in the doublecortin gene, who developed West syndrome at the age of 5 months. In both the cases, (123)I-iomazenil single photon emission computed tomography performed during infancy showed significant hyperfixation in the dysplastic lesions. This finding indicates the immaturity of the affected neurons and a gamma-aminobutyric acidergic involvement in epileptogenesis associated with malformations of cortical development during infancy.

Topics: Cerebral Cortex; Child, Preschool; Epilepsy; Flumazenil; Humans; Infant; Iodine Radioisotopes; Male; Nervous System Malformations; Tomography, Emission-Computed, Single-Photon

Since the neuroradiological features of patients with 22q11.2 deletion syndrome are not well-understood, examinations using functional imaging were performed in this study. Brain magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (MRS) were performed using a clinical 3-Tesla MR imager in 4 patients with 22q11.2 deletion syndrome (2 boys and 2 girls; aged 2-6 years.) and 20 age- and sex-matched healthy control subjects. Furthermore, interictal 123I-iomazenil (IMZ) single photon emission computed tomography (SPECT) was examined in 2 of the 4 patients. Among the 4 patients with 22q11.2 deletion syndrome, 2 patients showed polymicrogyria and 1 patient showed agyria. Those patients with brain malformations also showed abnormal brain artery patterns and decreased accumulation of IMZ in 123I-IMZ SPECT. Although all 4 patients showed epileptic discharges in their electroencephalograms (EEG), one patient with polymicrogyria had no seizure episodes. Decreases in γ-aminobutyric acid (GABA) corresponding to the areas of polymicrogyria and/or epileptic discharges in EEG were shown in all patients except for the patient with agyria. Although consistent evidence was not seen in patients with 22q11.2 deletion syndrome in this study, brain malformations and disturbances of the GABAergic nervous system would be underlying mechanisms of the neurodevelopmental abnormalities in this syndrome.

Topics: Case-Control Studies; Child; Child, Preschool; DiGeorge Syndrome; Electroencephalography; Epilepsy; Female; Flumazenil; gamma-Aminobutyric Acid; Humans; Hydrogen; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Malformations of Cortical Development; Radiography; Tomography, Emission-Computed, Single-Photon

(123)I-Iomazenil brain SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Although epileptogenic foci exhibit a decrease in (123)I-iomazenil accumulation, normal cerebral cortices often exhibit similar findings because of thin cortical ribbons, gray matter atrophy, or pathologic brain structures. In the present study, we created (123)I-iomazenil SPECT images corrected for gray matter volume using MRI and tested whether the detectability of the epileptogenic foci improved.. Seven patients (1 male patient and 6 female patients; mean age +/- SD, 34 +/- 17 y) with intractable epilepsy were surgically treated by resecting the cerebral cortex after surface electroencephalography. Histopathologic examination of the resected specimens and a good outcome after surgery indicated that the resected lesions were epileptogenic foci. These patients underwent (123)I-iomazenil SPECT and 3-dimensional T1-weighted MRI examinations before their operations. Each SPECT image was coregistered to the corresponding MR image, and its partial-volume effect (PVE) was corrected on a voxel-by-voxel basis with a smoothed gray matter distribution image. Four nuclear medicine physicians visually evaluated the (123)I-iomazenil SPECT images with and without the PVE correction. The SPECT count ratio of the suspected focus to the contralateral cerebral cortex was evaluated as an asymmetry index (%) based on the volume of interest.. The sensitivity, specificity, and accuracy of focus detection by visual assessment were higher after PVE correction (88%, 99%, and 98%, respectively) than before correction (50%, 92%, and 87%, respectively). The mean asymmetry index for the surgically resected lesions was significantly higher on the PVE-corrected SPECT images (22%) than on the PVE-uncorrected ones (16%) (P = 0.006).. MRI-based PVE correction for (123)I-iomazenil brain SPECT improves the sensitivity and specificity of the detection of cortical epileptogenic foci in patients with intractable epilepsy.

Topics: Adult; Artifacts; Brain; Epilepsy; Female; Flumazenil; Humans; Image Enhancement; Imaging, Three-Dimensional; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Clinical and experimental studies on focal cortical dysplasia (FCD) were carried out.. For the experimental study, an experimental FCD model of rats was developed. Twenty Wistar rats at 0-2 days after birth were used for the study. Kainic acid (KA) solution was injected stereotaxically into medial and lateral sites of the sensori-motor cortex. Bipolar electrodes were inserted in five rats. Their behavior and electroencephalogram (EEG) were recorded using a digital-video-EEG monitoring system. After observation periods of 1, 2, and 6 months, rats were perfused for pathological study. FCD was observed adjacent to the site of KA injection in all rats more than 1 month after the injection.. EEG recording demonstrated focal spike discharges in and around the site of injection. However, clinical seizure was not observed. Pathological studies showed decrease in GABA-A receptors and increase in GABA-B receptors not only in the lesion but also in perilesional areas. Fifteen surgical cases of FCD with intractable epilepsy were subjected to the clinical study. Neuro-imaging studies including high-resolution magnetic resonance imaging and single-photon emission computed tomography were performed. Conventional EEG studies demonstrated focal EEG abnormalities with epileptic phenomena. At surgery, intraoperative electrocorticography (ECoG) was performed to localize epileptic foci under neuroleptoanalgesia. Thirteen patients showed epileptiform discharges on preresection ECoG. All foci in non-eloquent areas were resected. Pathological studies including immunohistochemical staining were performed, and the characteristics of the FCD in relation to EEG findings were analyzed. Patients in whom total lesionectomy with complete focus resection was performed had favorable postoperative courses. Nine patients (64.3%) have been seizure-free with reduced medication, and significant improvement was achieved in two patients (14.3%). Electrophysiological examination revealed epileptogenecity not only in the lesions but also in perilesional areas. The immunohistochemical studies showed a decrease in GABA-A receptors and an increase in GABA-B receptors in both the lesions and perilesional areas, but N-methyl-D: -aspartate receptors were almost negative in both areas. Glutamate R1 was decreased in both areas, but glutamate R2 was increased in both areas. These findings support the results of a electrophysiological study.. In conclusion, not only the epileptic property of experimental focal cortical dysplasia but also perilesional epileptogenesis was demonstrated. These findings supported the results of surgery for patients with focal cortical dysplasia. In cases of FCD, total removal of the lesion and resection of the perilesional epileptic focus are needed for a good outcome.

Topics: Adolescent; Animals; Animals, Newborn; Autoradiography; Behavior, Animal; Brain Diseases; Brain Mapping; Cerebral Cortex; Child; Electroencephalography; Epilepsy; Female; Flumazenil; gamma-Aminobutyric Acid; Humans; Immunohistochemistry; Iodine Radioisotopes; Kainic Acid; Male; Nervous System Malformations; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate

Topics: Adolescent; Benzodiazepines; Child; Child, Preschool; Epilepsy; Female; Flumazenil; Humans; Infant; Male; Tomography, Emission-Computed, Single-Photon

To investigate changes in free benzodiazepine receptor density in response to repeated, long-term administration of diazepam in epilepsy, we assessed 125I-iomazenil (125I-IMZ) binding in a mouse model.. El mice were divided into two groups of 12 mice each which received either no diazepam (E1(D[-]) group) or 2 mg/kg of diazepam per week (El(D[+]) group). Nine ddY mice were used as a control. Once each week from the age of 5 to 19 weeks, the El mice received stimulation to produce epileptic seizures 20 minutes after receiving intraperitoneal injections. At 20 weeks of age, a total dose of 0.37 MBq of 125I-IMZ was injected in all mice and their brains were rapidly removed 3 hours later. The incidence of epileptic seizures at the age of 19 weeks and the autoradiograms of the brain were compared.. The incidence of epileptic seizures in response to weekly stimulation was significantly lower in the E1(D[+]) group than in the E1(D[-]) group (p < 0.001). The percent injected doses of 125I-IMZ per gram of tissue in the cortex, hippocampus and amygdala were significantly lower in the E1(D[+]) group than in the E1(D[-]) group (p < 0.05).. The results suggest that diazepam binds competitively to 125I-IMZ as an agonist to free benzodiazepine receptor sites in the cortex, hippocampus and amygdala and shows anticonvulsant effect in E1 mice.

Topics: Animals; Anticonvulsants; Autoradiography; Brain; Diazepam; Disease Models, Animal; Epilepsy; Flumazenil; Iodine Radioisotopes; Mice; Protein Binding; Receptors, GABA-A; Seizures; Time Factors

Central benzodiazepine receptor binding was studied in spontaneously epileptic rats (SER) and in their parent strain. Kyoto-Wistar (KW) rats, by ex vivo quantitative autoradiography with [125I]iomazenil. Thirteen-week-old SER developed tonic and absence-like seizures following mild stimulation by tapping at 5 min before injection of the radioligand. When compared with age-matched KW rats, a significant 76% elevation of radioactivity was observed in the SER hippocampus, while there was no difference in hippocampal blood flow obtained using [125I]N-isopropyl-p-iodoamphetamine. Since benzodiazepine receptors act to enhance inhibitory GABA transmission, this finding suggests a possible mechanism for seizure-induced enhancement of inhibition.

Topics: Animals; Autoradiography; Brain; Cerebrovascular Circulation; Epilepsy; Flumazenil; Iodine Radioisotopes; Kinetics; Male; Organ Specificity; Rats; Rats, Inbred WKY; Rats, Mutant Strains; Receptors, GABA-A; Species Specificity; Time Factors

To clarify experimentally which of benzodiazepine (BZ) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the BZ receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethyl-propyleneamine oxime (99mTc-HMPAO). In visual analysis of brain slices extracted after the intravenous injection of the double tracer following the kindling completion, 125I-Iomazenil accumulation was more markedly and extensively decreased in the kindled right CA1 region mimicking a primary epileptic focus than 99mTc-HMPAO accumulation. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities which consisted only of tissue damage corresponding to electrode track in the right CA1. These results suggest that BZ receptor imaging is more sensitive in the detection of epileptic foci than rCBF imaging and, therefore, that BZ receptor imaging is useful in clinical epilepsy.

Topics: Animals; Autoradiography; Cerebrovascular Circulation; Epilepsy; Flumazenil; Hippocampus; Iodine Radioisotopes; Kindling, Neurologic; Male; Rabbits; Receptors, GABA-A; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

The flumazenil analogue, Ro 16-0154, a benzodiazepine partial inverse agonist, has been labeled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in the human brain. The purified 123I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacologic properties were comparable to those of flumazenil. The biodistribution in rats (1 hr postinjection) resulted in a high brain-to-blood ratio of 16. Clinical studies revealed images of the benzodiazepine receptor density in the brain. Since the receptor labeling was markedly reduced by injection of flumazenil, it was considered to be specific. Storage defects due to pathologic cerebral blood flow and changed receptor density were detected; this shows the potential usefulness of the substance for diagnostic purposes, e.g., the differential diagnosis of various forms of epilepsy.

Topics: Animals; Brain; Cerebrovascular Circulation; Drug Stability; Epilepsy; Female; Flumazenil; Humans; In Vitro Techniques; Iodine Radioisotopes; Rats; Rats, Inbred Strains; Receptors, GABA-A; Tissue Distribution; Tomography, Emission-Computed, Single-Photon