Extended studies of the striatal uptake of 99mTc-NC100697 in healthy volunteers.

This study evaluates a new formulation of a (99m)Tc-labeled tropane derivate, (99m)Tc-NC100697, in a human volunteer study. METHODS: Eighty healthy subjects (39 females, 41 males) underwent MRI and SPECT (injected dose [mean +/- SD], 10.6 +/- 1.4 MBq/kg). Forty subjects were investigated 30, 90, 180, 240, 360, and 480 min after injection, and another 40 subjects were imaged 240 min after injection. Specific striatal binding was assessed using 3 different approaches: 3-dimensional volumes of interest (VOIs) drawn on the coregistered MRI scans, manually placed predefined 2-dimensional regions of interest (ROIs), and observer-independent fully automated 3-dimensional VOI analyses based on coregistration of scans with a mean template of controls. Specific striatal dopamine transporter (DAT) binding was estimated for cohorts of ages of 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 y. The relationship between age and DAT binding was analyzed with linear, "broken-stick," exponential, and logarithmic regression. RESULTS: Serial SPECT scans revealed increasing values of specific DAT binding over time. Consideration of all important variables suggests an optimum imaging time at 4 h after injection. Average DAT binding for the total population was 1.1 +/- 0.2 (striatum), 1.3 +/- 0.2 (caudate), and 1.1 +/- 0.2 (putamen), with mean putamen-to-caudate ratios of 0.83 +/- 0.08 (manual 2-dimensional ROI method). A significant age dependency of striatal DAT binding, best described by a broken-stick (break-point age, 48 y) or logarithmic regression (both r = 0.76), with a lower decline observed in older than in younger subjects. Female subjects presented with slightly higher binding ratios than male subjects, more pronounced in pre- than in postmenopausal women. There was a high correlation between the 3 semiquantitative evaluations. CONCLUSION: The current study has demonstrated the effective use of (99m)Tc-NC100697 for estimating presynaptic striatal DAT binding. The comparison of different semiquantification methods showed that in clinical routine work, this tracer can be reliably evaluated without individual MRI data. Age and a slight sex dependency (especially in premenopausal women) of (99m)Tc-NC100697 binding should be taken into consideration. The data generated in this phase 1 study provides a basis for an age- and sex-matched normal database.     

Multiple swallow test for the quantitative and qualitative evaluation of esophageal motility disorders

Esophageal motility was evaluated from the analysis of six consecutive swallows. A sum image was generated comprising the representative information of an entire study. Calculation of emptying rates and characterization of the bolus behavior was performed from the sum image and the single swallow data. In 86 patients investigated, liquid and solid-phase studies showed a remarkable variation of single swallow data in normals (relative variation coefficient for liquid: 10%, solid: 14%), which were even higher (p less than 0.001) in patients with disorders (liquid: 31%, solid: 25%). As sum images compensate for this intra-individual variation, false-positive (liquid: 16%, solid: 25%) or negative single swallow findings (liquid: 36%, solid: 27%) are reduced. Qualitative analysis of condensed sum images provided characteristic image patterns representing different pathophysiologic aspects. Since the method introduced better discriminates between normal and pathologic function, it may enhance diagnostic accuracy.     

Hepatitis C: incidence and knowledge among Brazilian dentists

OBJECTIVES: To evaluate the incidence of Hepatitis C among dentists from the city of Piracicaba-SP--Brazil, and also to analyze the knowledge of this disease among these health care workers. DESIGN: Two hundred and sixty-seven dentists completed a questionnaire and supplied a sample of blood for serologic testing for hepatitis C virus (HCV). RESULTS: Only one participant was positive for HCV, representing 0.4% of total. There was a lack of knowledge of this disease among dentists. CONCLUSIONS: There is an occupational risk of infection for HCV in dentistry and there is a need to make professionals aware of it.     

Compensation for cranial spill-in into the cerebellum improves quantitation of striatal dopamine D₂/₃ receptors in rats with prolonged [¹⁸F]-DMFP infusions

The condition of steady‐state receptor binding in positron emission tomography (PET) studies is best obtained through the use of a bolus plus steady‐infusion paradigm. This is a particularly important consideration in the context of in vivo competition studies, where a pharmacological challenge can be administered during the interval of steady‐state ligand binding, as in the case of [¹¹C]‐raclopride studies with amphetamine challenge. However, the short half‐life of ¹¹C imposes limits on the practical duration of constant infusions. Therefore, we chose to test [¹⁸F]‐DMFP as a tracer for dopamine D_2/3 receptors in rat striatum in the paradigm. Using a conventional bolus injection, the [¹⁸F]‐DMFP BP_ND was 3.8 in striatum of anesthetized rats. When followed by a constant infusion, we obtained quasi‐stable BP_ND estimates of 4.5 within an interval of 45 min. During infusions lasting up to 4 h, BP_ND declined progressively. This seemed due to the progressive spill‐in of radioactivity from the cranium to the cerebellum reference region, despite optimized iterative reconstruction of the images. Therefore, we propose a new concept of compensation for this spill‐in effect using pharmacokinetic considerations, without requiring high‐resolution anatomical images. Challenge with amphetamine (1 and 4 mg/kg) evoked an ～25% reduction in BP_ND. There was no clear evidence of dose‐dependence in the striatal‐binding changes, despite the considerably greater physiological effect, as documented by ECG. Thus, the general applicability of the bolus plus infusion method with [¹⁸F]‐DMFP for small animal studies is impeded by the substantial labeling of the cranium. The cranial uptake was linear, indicating first‐order kinetics for the enzymatic defluorination of the tracer. Based on this phenomenon, we developed an analytic method compensating for the effects of progressive cranial labeling on the estimation of specific binding in striatum. Synapse, 2012. © 2012 Wiley Periodicals, Inc.     

In vivo effects of olanzapine on striatal dopamine D(2)/D(3) receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study.

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D(2)/D(3) receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [(123)I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [(123)I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrence of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [(123)I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D(2)/D(3) receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D(2)/D(3) receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D(2)/D(3) receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D(2)/D(3) availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D(2)/D(3) striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D(2)/D(3) receptor affinity and a similar 5HT(2) receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D(2)/D(3) receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D(2)/D(3) and 5HT(2) receptor antagonism.     

In vivo effects of olanzapine on striatal dopamine D2/D3 receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D₂/D₃ receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [¹²³I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [¹²³I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrance of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [¹²³I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D₂/D₃ receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR–BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D₂/D₃ receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR–BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D₂/D₃ receptor availability revealed an exponential dose-response relationship (r=–0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D₂/D₃ availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D₂/D₃ striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D₂/D₃ receptor affinity and a similar 5HT₂ receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D₂/D₃ receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D₂/D₃ and 5HT₂ receptor antagonism. Received 6 March 1999 / in revised form 11 April 1999