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Axel Rominger Erika Wagner Erik Mille Guido Böning Mouna Esmaeilzadeh Björn Wängler Franz‐Josef Gildehaus Sebastian Nowak Ariane Bruche Klaus Tatsch Peter Bartenstein Paul Cumming 《Synapse (New York, N.Y.)》2010,64(4):313-322
Aim . Molecular imaging studies with benzamide radioligands can reveal competition from endogenous binding at D2/3‐receptors in living brain. However, single photon emission computed tomography (SPECT) methods suffer from limited spatial resolution, and [11C]‐labeled ligands are only available at positron emission tomography (PET) research sites with cyclotron‐radiochemistry facilities, whereas [18F] can be transported, due to its longer physical half‐life. Therefore, we endeavored to characterize the vulnerabilities of the benzamide antagonist [18F]desmethoxyfallypride (DMFP) and its high‐affinity congener [18F]fallypride (FP) to competition from endogenous dopamine in living mouse brain. Methods . Groups of awake mice were pretreated with saline, amphetamine (10 mg/kg), or reserpine (5 mg/kg), followed by i.v. tracer injections. Mice were killed at 2.5–90 min (DMFP) or 2.5–180 min (FP) circulation times. Brains were dissected and regional radioactivity concentration measured by gamma counting. Other groups of mice were anesthetized for dynamic microPET recordings with DMFP or FP. Binding potentials (BPND) were calculated using cerebellum as reference region. Results . With 90‐min circulation, DMFP BPND in striatum was 2.4 by dissection and 2.2 by microPET, which showed a 62% decrease in response to amphetamine‐evoked dopamine release and a 33% increase after reserpine‐evoked dopamine depletion. With 120‐min circulation, FP BPND in striatum was 24.1 by dissection and 9.2 by microPET, which showed a 31% decrease in the amphetamine group, but no effect of reserpine. Dissection showed similar sensitivities for FP binding, but only a 29% amphetamine‐evoked reduction for DMFP. Conclusions . Relative to gold standard ex vivo results, microPET estimates of DMFP BPND were unbiased, whereas FP BPND in striatum was substantially underestimated. Both tracers proved suitable for revealing pharmacologically evoked changes in competition at D2/3‐receptors in striatum of living mice. Synapse 64:313–322, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Matthew D Walker Katherine Dinelle Rick Kornelsen Nathan V Lee Qing Miao Mike Adam Christine Takhar Edwin Mak Michael Schulzer Matthew J Farrer Vesna Sossi 《Journal of cerebral blood flow and metabolism》2015,35(8):1331-1338
Neuroinflammation in the aging rat brain was investigated using [11C]PBR28 microPET (positron emission tomography) imaging. Normal rats were studied alongside LRRK2 p.G2019S transgenic rats; this mutation increases the risk of Parkinson''s disease in humans. Seventy [11C]PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of VT. In vitro autoradiography was also performed. PBR28 uptake increased with age, without differences between nontransgenic and transgenic rats. In 12 months of aging (4 to 16 months), standard uptake value (SUV) increased by 56% from 0.44 to 0.69 g/mL, whereas VT increased by 91% from 30 to 57 mL/cm3. Standard uptake value and VT were strongly correlated (r=0.52, 95% confidence interval (CI)=0.31 to 0.69, n=37). The plasma free fraction, fp, was 0.21±0.03 (mean±standard deviation, n=53). In vitro binding increased by 19% in 16 months of aging (4 to 20 months). The SUV was less variable across rats than VT; coefficients of variation were 13% (n=27) and 29% (n=12). The intraclass correlation coefficient for SUV was 0.53, but was effectively zero for VT. These data show that [11C]PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain. 相似文献
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Here we present the first demonstration that 2-deoxy-2[18F]fluoro-D-glucose (18FDG) and micro Positron Emission Tomography (microPET) can be used successfully to monitor regional changes in brain metabolism during acute seizure induction in C57Bl/6 mice. These longitudinal studies show a significant increase in 18FDG uptake in the hippocampus (33.2%) which correlates directly with seizure severity (R2=0.86). 18FDG microPET can potentially be used to monitor the development of TLE in mouse models from the acute phase of status epilepticus to the chronic phase of spontaneous recurrent seizures. These studies provide a foundation upon which we can begin to identify genetic contributions to the metabolic signature of TLE in mice, since many transgenics are in the C57Bl/6 background strain. 相似文献
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Xuan Zhang Qi Yin Marc Berridge Che Wang 《journal of environmental science and health part c-environmental carcinogenesis & ecotoxicology reviews》2013,31(3):113-124
Molecular imaging has been widely applied in preclinical research. Among these new molecular imaging modalities, microPET imaging can be utilized as a very powerful tool that can obtain the measurements of multiple biological processes in various organs repeatedly in a same subject. This review discusses how this new approach provides noninvasive biomarker for neurotoxicology research and summarizes microPET findings with multiple radiotracers on the variety of neurotoxicity induced by toxic agents in both the rodent and the nonhuman primate brain. 相似文献
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Zhou GJ Zhang H Zhi SD Jiang GP Wang J Zhang M Gan JX Xu SW Jiang GY 《Acta pharmacologica Sinica》2007,28(10):1585-1590
Aim: To evaluate the protective effect of oral raloxifene on acute lung injury. Methods: Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups: the raloxifene-lipopolysaccharide (LPS)-HCI group (n=10), the LPS-raloxifene-HCl group (n=10), and the placebo group (n=10). All the rats were injected intraperitoneally (ip) with 5 mg/kg LPS, and raloxifene (30 mg/kg) was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal (IT) injection ofHCl (pH 1.2; 0.5 mL/kg). The mean arterial pressure (MAP) and blood gas concentrations were measured. Fifteen rats (5 in each group, respectively) underwent a micro positron emission tomography (microPET) scan of the thorax 4 h after HCI instillation. The wet/dry (W/D) weight ratio determination and histopathological examination were also performed. Results: The rats in the LPS-raloxifene-HCl group had a lower [^18F]fluorodeoxyglucose uptake compared with the rats in the placebo group (4.67±1.33 vs 9.01±1.58, respectively, P〈0.01). The rats in the LPS-raloxifene-HCl group also had a lower histological lung injury score (8.20± 1.23 vs 12.6±0.97, respectively, P〈0.01) and W/D weight ratio (5.335±0.198 vs 5.886±0.257, respectively, P〈0.01) compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure (MAP) compared to the placebo group. Conclusion: Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HCI IT instillation. 相似文献
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Axel Rominger Erik Mille Guido Böning Björn Wängler Franz Josef Gildehaus Cornelia Arszol Peter Bartenstein Paul Cumming 《Synapse (New York, N.Y.)》2010,64(8):654-657
Aim. To test for α2 adrenergic modulation of dopamine D2/3 receptor availability in striatum of living mice using the high‐affinity ligand [18F]fallypride and microPET. Methods. Groups of anesthetized mice were pretreated with saline, the α2‐agonist clonidine (1 mg/kg), and the α2‐antagonists RX821002 (1 mg/kg) and yohimbine (1 mg/kg). Dynamic microPET recordings lasting 120 min were then initiated upon i.v. tracer injection of [18F]fallypride. Parametric maps of [18F]fallypride binding potential (BPND) were calculated using the Logan method, with cerebellum serving as the reference region. Results. Mean striatal [18F]fallypride BPND was 10.6 ± 1.7 in the saline control animals, 8.9 ± 1.7 (?16%; P < 0.05) in the RX821002 group, 8.3 ± 2.6 (?22%; P < 0.05) in the yohimbine group and 10.3 ± 2.2 (n.s.) in the clonidine group. Conclusions. These findings are consistent with a tonic inhibition of dopamine release by α2 adrenergic receptors, such that α2 blockade increased the competition from endogenous dopamine at D2/3 receptors, thus reducing the [18F]fallypride BPND by about 20%. Absent effects of clonidine suggest a ceiling effect in the tonic inhibition of dopamine release. This in vivo PET evidence for α2/dopaminergic interaction may be relevant to putative actions of atypical antipsychotic medications via adrenergic receptors. Synapse, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
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Small Animal Imaging Center Design: The Facility at the UCLA Crump Institute for Molecular Imaging 总被引:2,自引:2,他引:0
David?B.?StoutEmail author Arion?F.?Chatziioannou Timothy?P.?Lawson Robert?W.?Silverman Sanjiv?S.?Gambhir Michael?E.?Phelps 《Molecular imaging and biology》2005,7(6):393-402
Purpose
The growing number of mouse and rat experiments, coupled with advances in small-animal imaging systems such as microPET®, optical, microCAT?, microMR, ultrasound and microSPECT, has necessitated a common technical center for imaging small animals.Procedures
At the UCLA Crump Institute for Molecular Imaging, we have designed and built a facility to support the research interests of a wide range of investigators from multiple disciplines. Requirements to satisfy both research and regulatory oversight have been critically examined. Support is provided for investigator training, study scheduling, data acquisition, archiving, image display, and analysis.Results
The center has been in operation for more than 18 months, supporting more than 13,000 individual imaging procedures.Conclusions
We have created a facility that maximizes our resource utilization while providing optimal investigator support, as well as the means to continually improve the quality and diversity of the science by integrating physical and biological sciences.9.
C.L. ZAVALETA W.T. PHILLIPS Y.C. BRADLEY† L.M. McMANUS‡ P.A. JERABEK§ & B.A. GOINS 《International journal of gynecological cancer》2007,17(2):407-417
MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose ((18)F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 microCi) of (18)F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of (18)F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of (18)F-FDG throughout the peritoneal cavity of tumor rats (mean SUV=4.64) compared with control rats (mean SUV=1.03). Ascites gathered from tumor-bearing rats had increased (18)F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. (18)F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using (18)F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model. 相似文献
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Eun Sil Shin Onyou Hwang Yu-Shik Hwang Jun-Kyo Francis Suh Young Il Chun Sang Ryong Jeon 《Journal of Korean Neurosurgical Society》2014,56(5):383-389