ro-16-0154 and Parkinson-Disease

123I-iomazenil is a partial inverse agonist of central-type benzodiazepine receptors (BZRs). BZR and the gamma-aminobutylic acid(GABA) receptor comprise a receptor complex in the cerebral cortex. Therefore, 123I-iomazenil SPECT will provide indirect information of the GABA receptor. Since the GABA-ergic system has been reported to modulate the dopaminergic system, the impairment of GABA/BZR may affect parkinsonian symptoms. However, there are few reports on Parkinson's disease(PD) regarding the impairment of GABA/BZR in the cerebral cortex. We found a correlation between motor disability and decrease in 123I-iomazenil uptake in the cerebral cortex, suggesting that BZR in the cerebral cortex of patients with PD may be impaired in proportion to the severity of the disease. In addition, the 123I-iomazenil image is, in part, different from the perfusion image. Therefore, 123I-iomazenil SPECT may give an additional information on the pathophysiology of PD.

Topics: Amphetamines; Animals; Cerebral Cortex; Flumazenil; Humans; Iodine Radioisotopes; Iofetamine; Parkinson Disease; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

123I-iomazenil is a partial inverse agonist of central-type benzodiazepine receptor (BZR). Single photon emission tomography (SPECT) using 123I-iomazenil was performed in 15 patients with Parkinson's disease (PD). SPECT images were obtained 3 hours after intravenous injection of 167 MBq of 123I-iomazenil. The ratio of 123I-iomazenil SPECT count in the cerebral cortex to that in the cerebellum was calculated as the binding potential index (BPI). The BPIs in the lower frontal, temporal, parietal and occipital cortices correlated with the motor disability evaluated by Yahr's stage. The BPI in the upper frontal cortex showed the same tendency as in the other regions but did not reach a significant level. These results suggest that BZR in the cerebral cortex of patients with PD may be impaired in proportion to the severity of the disease and that 123I-iomazenil SPECT is useful for evaluating the pathophysiological condition in PD.

Topics: Aged; Aged, 80 and over; Cerebral Cortex; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Parkinson Disease; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

"Delayed" single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0-3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [123I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.

Topics: Alzheimer Disease; Brain; Case-Control Studies; Cerebral Infarction; Computer Simulation; Dementia, Vascular; Flumazenil; Humans; Iodine Radioisotopes; Male; Parkinson Disease; Receptors, GABA-A; Time Factors; Tomography, Emission-Computed, Single-Photon