Molecular Imaging最新文献

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Preclinical Multimodal Molecular Imaging Using 18F-FDG PET/CT and MRI in a Phase I Study of a Knee Osteoarthritis in In Vivo Canine Model. 使用18F-FDG PET/CT和MRI进行临床前多模态分子成像在犬体内膝关节骨关节炎模型中的I期研究。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117697443
Maria I Menendez, Bianca Hettlich, Lai Wei, Michael V Knopp
{"title":"Preclinical Multimodal Molecular Imaging Using <sup>18</sup>F-FDG PET/CT and MRI in a Phase I Study of a Knee Osteoarthritis in In Vivo Canine Model.","authors":"Maria I Menendez,&nbsp;Bianca Hettlich,&nbsp;Lai Wei,&nbsp;Michael V Knopp","doi":"10.1177/1536012117697443","DOIUrl":"https://doi.org/10.1177/1536012117697443","url":null,"abstract":"<p><p>The aim of this study was to use a multimodal molecular imaging approach to serially assess regional metabolic changes in the knee in an in vivo anterior cruciate ligament transection (ACLT) canine model of osteoarthritis (OA). Five canine underwent ACLT in one knee and the contralateral knee served as uninjured control. Prior, 3, 6, and 12 weeks post-ACLT, the dogs underwent <sup>18</sup>F-fluoro-d-glucose (<sup>18</sup>F-FDG) positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI). The MRI was coregistered with the PET/CT, and 3-dimensional regions of interest (ROIs) were traced manually and maximum standardized uptake values (SUV<sub>max</sub>) were evaluated. <sup>18</sup>F-fluoro-d-glucose SUV<sub>max</sub> in the ACLT knee ROIs was significantly higher compared to the uninjured contralateral knees at 3, 6, and 12 weeks. Higher <sup>18</sup>F-FDG uptake observed in ACLT knees compared to the uninjured knees reflects greater metabolic changes in the injured knees over time. Knee <sup>18</sup>F-FDG uptake in an in vivo ACLT canine model using combined PET/CT and MRI demonstrated to be highly sensitive in the detection of metabolic alterations in osseous and nonosteochondral structures comprising the knee joint. <sup>18</sup>F-fluoro-d-glucose appeared to be a capable potential imaging biomarker for early human knee OA diagnosis, prognosis, and management.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117697443"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117697443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Commentary on "A Microfluidic Platform to Design Crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for Enhanced MRI". “设计用于增强MRI的交联透明质酸纳米颗粒(cHANPs)的微流控平台”评论。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117706237
Maria Russo, Paolo Bevilacqua, Paolo Antonio Netti, Enza Torino
{"title":"Commentary on \"A Microfluidic Platform to Design Crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for Enhanced MRI\".","authors":"Maria Russo,&nbsp;Paolo Bevilacqua,&nbsp;Paolo Antonio Netti,&nbsp;Enza Torino","doi":"10.1177/1536012117706237","DOIUrl":"https://doi.org/10.1177/1536012117706237","url":null,"abstract":"<p><p>Strategies to enhance the relaxometric properties of gadolinium (Gd)-based contrast agents (CAs) for magnetic resonance imaging (MRI), without the chemical modification of chelates, have recently had a strong impact on the diagnostic field. We have taken advantage of the interaction between Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and the hydrogel structure of hyaluronic acid to design cross-linked hyaluronic acid nanoparticles down to 35 nm for use in MRI applications. The proposed bioformulations enable the control of the relaxometric properties of CAs, thus boosting the relaxation rate of T1. Our results led us to identify this approach as an adjustable scenario to design intravascularly injectable hydrogel nanoparticles entrapping Gd-DTPA. This approach overcomes the general drawbacks of clinically approved CAs having poor relaxivity and toxic effects.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117706237"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117706237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 10
Molecular Imaging of IGF-1R in Cancer. 肿瘤中IGF-1R的分子成像。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117736648
Yingying Sun, Xilin Sun, Baozhong Shen
{"title":"Molecular Imaging of IGF-1R in Cancer.","authors":"Yingying Sun,&nbsp;Xilin Sun,&nbsp;Baozhong Shen","doi":"10.1177/1536012117736648","DOIUrl":"https://doi.org/10.1177/1536012117736648","url":null,"abstract":"<p><p>The important role of insulin-like growth factor 1 receptor (IGF-1R) in malignant tumors has been well established. Increased IGF-1R activity promotes cancer cell proliferation, migration, and invasion and is associated with tumor metastasis, treatment resistance, poor prognosis, and shortened survival in patients with cancer. However, while IGF-1R has become a promising target for cancer therapy, IGF-1R-targeted therapy is ineffective in unselected patients. It is therefore essential to evaluate IGF-1R expression before treatment in order to identify responsive patients, monitor therapy efficacy, and estimate prognosis. Insulin-like growth factor 1 receptor molecular imaging is an optimal method for assessing the expression of IGF-1R in vivo accurately and noninvasively. In this review, we will summarize the current status of IGF-1R molecular imaging in cancer, in which 5 major classes of ligands that have been developed for noninvasive IGF-1R molecular imaging will be discussed: natural ligands, monoclonal antibodies, antibody fragments, affibodies, and small molecules. For decades, IGF-1R molecular imaging is studied in full swing and more effort is needed in the future.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117736648"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117736648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35638615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 26
Ex Vivo and In Vivo Noninvasive Imaging of Epidermal Growth Factor Receptor Inhibition on Colon Tumorigenesis Using Activatable Near-Infrared Fluorescent Probes. 利用可激活的近红外荧光探针研究表皮生长因子受体抑制结肠肿瘤发生的体内和体外无创成像。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117729044
Shengli Ding, Randall E Blue, Emily Moorefield, Hong Yuan, Pauline K Lund
{"title":"Ex Vivo and In Vivo Noninvasive Imaging of Epidermal Growth Factor Receptor Inhibition on Colon Tumorigenesis Using Activatable Near-Infrared Fluorescent Probes.","authors":"Shengli Ding,&nbsp;Randall E Blue,&nbsp;Emily Moorefield,&nbsp;Hong Yuan,&nbsp;Pauline K Lund","doi":"10.1177/1536012117729044","DOIUrl":"https://doi.org/10.1177/1536012117729044","url":null,"abstract":"<p><strong>Background: </strong>Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection.</p><p><strong>Objective: </strong>To test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in Apc<sup>Min/+</sup> mice.</p><p><strong>Methods: </strong>The AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet. These and Apc<sup>Min/+</sup> mice were given cathepsin-activatable probes (ProSense 680) before imaging. In vivo imaging was performed using quantitative tomographic NIRF imaging. Ex vivo imaging and histologic examination were performed. Dual imaging by micro computed tomography (CT) and 3D NIRF imaging was used to verify tumor location.</p><p><strong>Results: </strong>Tumor load reduction by EGFR inhibition was detected ex vivo using cathepsin B probes. In vivo imaging revealed intense activation of probes only in large tumors. Dual imaging with microCT and 3D NIRF imaging improved tumor detection in vivo.</p><p><strong>Conclusions: </strong>The 3-D NIRF imaging with ProSense 680 can detect and quantify drug effects on colon tumors ex vivo. The NIRF imaging with ProSense 680 probe has limitations as a valid nonendoscopic method for intestinal tumor detection. Combing with other imaging modalities will improve the specificity and sensitivity of intestinal tumor detection in vivo.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117729044"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117729044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35336739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Imaging Hepatocellular Carcinoma With 68Ga-Citrate PET: First Clinical Experience. 68ga -柠檬酸PET成像肝细胞癌:首次临床经验。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117723256
Carina Mari Aparici, Spencer C Behr, Youngho Seo, R Kate Kelley, Carlos Corvera, Kenneth T Gao, Rahul Aggarwal, Michael J Evans
{"title":"Imaging Hepatocellular Carcinoma With <sup>68</sup>Ga-Citrate PET: First Clinical Experience.","authors":"Carina Mari Aparici,&nbsp;Spencer C Behr,&nbsp;Youngho Seo,&nbsp;R Kate Kelley,&nbsp;Carlos Corvera,&nbsp;Kenneth T Gao,&nbsp;Rahul Aggarwal,&nbsp;Michael J Evans","doi":"10.1177/1536012117723256","DOIUrl":"https://doi.org/10.1177/1536012117723256","url":null,"abstract":"<p><p>While cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging is the primary method for diagnosing hepatocellular carcinoma (HCC), they provide little biological insight into this molecularly heterogeneous disease. Nuclear imaging tools that can detect molecular subsets of tumors could greatly improve diagnosis and management of HCC. To this end, we conducted a patient study to determine whether HCC can be resolved using <sup>68</sup>Ga-citrate positron emission tomography (PET). One patient with recurrent HCC was injected with 300 MBq of <sup>68</sup>Ga-citrate and imaged with PET/CT 249 minutes post injection. Four (28%) of 14 hepatic lesions were avid for <sup>68</sup>Ga-citrate. One extrahepatic lesion was not PET avid. The average maximum standardized uptake value (SUV<sub>max</sub>) for the lesions was 7.2 (range: 6.2-8.4), while the SUV<sub>max</sub> of the normal liver parenchyma was 4.7 and blood pool was 5.7. The avid lesions were not significantly larger than the quiescent lesions, and a prior contrast CT showed uniform enhancement among the lesions, suggesting that tumor signals are due to specific binding of the radiotracer to the transferrin receptor, rather than enhanced vascularity in the tumor microenvironment. Further studies are required in a larger patient cohort to verify the molecular basis of radiotracer uptake and the clinical utility of this tool.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117723256"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117723256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35392453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT. 水解酶的PET和SPECT分子成像。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117717852
Brian P Rempel, Eric W Price, Christopher P Phenix
{"title":"Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.","authors":"Brian P Rempel,&nbsp;Eric W Price,&nbsp;Christopher P Phenix","doi":"10.1177/1536012117717852","DOIUrl":"https://doi.org/10.1177/1536012117717852","url":null,"abstract":"<p><p>Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117717852"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117717852","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35420535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential. 以磷脂酰丝氨酸为靶点的脑肿瘤纳米治疗剂及其治疗潜力。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117708722
Lulu Wang, Amyn A Habib, Akiva Mintz, King C Li, Dawen Zhao
{"title":"Phosphatidylserine-Targeted Nanotheranostics for Brain Tumor Imaging and Therapeutic Potential.","authors":"Lulu Wang,&nbsp;Amyn A Habib,&nbsp;Akiva Mintz,&nbsp;King C Li,&nbsp;Dawen Zhao","doi":"10.1177/1536012117708722","DOIUrl":"https://doi.org/10.1177/1536012117708722","url":null,"abstract":"<p><p>Phosphatidylserine (PS), the most abundant anionic phospholipid in cell membrane, is strictly confined to the inner leaflet in normal cells. However, this PS asymmetry is found disruptive in many tumor vascular endothelial cells. We discuss the underlying mechanisms for PS asymmetry maintenance in normal cells and its loss in tumor cells. The specificity of PS exposure in tumor vasculature but not normal blood vessels may establish it a useful biomarker for cancer molecular imaging. Indeed, utilizing PS-targeting antibodies, multiple imaging probes have been developed and multimodal imaging data have shown their high tumor-selective targeting in various cancers. There is a critical need for improved diagnosis and therapy for brain tumors. We have recently established PS-targeted nanoplatforms, aiming to enhance delivery of imaging contrast agents across the blood-brain barrier to facilitate imaging of brain tumors. Advantages of using the nanodelivery system, in particular, lipid-based nanocarriers, are discussed here. We also describe our recent research interest in developing PS-targeted nanotheranostics for potential image-guided drug delivery to treat brain tumors.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117708722"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117708722","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35122877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors. 异种移植肿瘤中花青素7标记甘露糖对肿瘤相关巨噬细胞的靶向成像
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012116689499
Chong Jiang, Huawei Cai, Xiaodong Peng, Ping Zhang, Xiaoai Wu, Rong Tian
{"title":"Targeted Imaging of Tumor-Associated Macrophages by Cyanine 7-Labeled Mannose in Xenograft Tumors.","authors":"Chong Jiang,&nbsp;Huawei Cai,&nbsp;Xiaodong Peng,&nbsp;Ping Zhang,&nbsp;Xiaoai Wu,&nbsp;Rong Tian","doi":"10.1177/1536012116689499","DOIUrl":"https://doi.org/10.1177/1536012116689499","url":null,"abstract":"<p><p>Mannose receptor is considered as a hallmark of M2-oriented tumor-associated macrophages (TAMs), but its utility in TAMs was rarely reported. Therefore, deoxymannose (DM), a high-affinity ligand of mannose receptor, was labeled with near-infrared dye cyanine 7 (Cy7), and its feasibility of targeted imaging on TAMs was evaluated in vitro and in vivo. The Cy7-DM was synthesized, and its binding affinity with induced TAMs in vitro, whole-body imaging in xenograft tumor mouse model in vivo, and the cellular localization in dissected tissues were evaluated. We demonstrated a high uptake of Cy7-DM by induced M2 macrophages and TAMs in tumor tissues. In vivo near-infrared live imaging visualized abundant TAMs in tumor lesions instead of inflammatory sites by Cy7-DM imaging, and the quantity of Cy7-DM signals in tumors was significantly higher than that shown in inflammatory sites from 1 to 8 hours of imaging. Our results suggest that mannose could rapidly and specifically target TAMs and is a promising candidate for targeted diagnosis of tumor with rich TAMs.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012116689499"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012116689499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35125052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 28
The Search for a Subtype-Selective PET Imaging Agent for the GABAA Receptor Complex: Evaluation of the Radiotracer [11C]ADO in Nonhuman Primates. 寻找GABAA受体复合物亚型选择性PET显像剂:对非人灵长类动物放射性示踪剂[11C]ADO的评价。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117731258
Shu-Fei Lin, Frederic Bois, Daniel Holden, Nabeel Nabulsi, Richard Pracitto, Hong Gao, Michael Kapinos, Jo-Ku Teng, Anupama Shirali, Jim Ropchan, Richard E Carson, Charles S Elmore, Neil Vasdev, Yiyun Huang
{"title":"The Search for a Subtype-Selective PET Imaging Agent for the GABA<sub>A</sub> Receptor Complex: Evaluation of the Radiotracer [<sup>11</sup>C]ADO in Nonhuman Primates.","authors":"Shu-Fei Lin,&nbsp;Frederic Bois,&nbsp;Daniel Holden,&nbsp;Nabeel Nabulsi,&nbsp;Richard Pracitto,&nbsp;Hong Gao,&nbsp;Michael Kapinos,&nbsp;Jo-Ku Teng,&nbsp;Anupama Shirali,&nbsp;Jim Ropchan,&nbsp;Richard E Carson,&nbsp;Charles S Elmore,&nbsp;Neil Vasdev,&nbsp;Yiyun Huang","doi":"10.1177/1536012117731258","DOIUrl":"https://doi.org/10.1177/1536012117731258","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The myriad physiological functions of γ-amino butyric acid (GABA) are mediated by the GABA-benzodiazepine receptor complex comprising of the GABA&lt;sub&gt;A&lt;/sub&gt;, GABA&lt;sub&gt;B&lt;/sub&gt;, and GABA&lt;sub&gt;C&lt;/sub&gt; groups. The various GABA&lt;sub&gt;A&lt;/sub&gt; subunits with region-specific distributions in the brain subserve different functional and physiological roles. For example, the sedative and anticonvulsive effects of classical benzodiazepines are attributed to the α&lt;sub&gt;1&lt;/sub&gt; subunit, and the α&lt;sub&gt;2&lt;/sub&gt; and α&lt;sub&gt;3&lt;/sub&gt; subunits mediate the anxiolytic effect. To optimize pharmacotherapies with improved efficacy and devoid of undesirable side effects for the treatment of anxiety disorders, subtype-selective imaging radiotracers are required to assess target engagement at GABA sites and determine the dose-receptor occupancy relationships. The goal of this work was to characterize, in nonhuman primates, the in vivo binding profile of a novel positron emission tomography (PET) radiotracer, [&lt;sup&gt;11&lt;/sup&gt;C]ADO, which has been indicated to have functional selectivity for the GABA&lt;sub&gt;A&lt;/sub&gt; α&lt;sub&gt;2&lt;/sub&gt;/α&lt;sub&gt;3&lt;/sub&gt; subunits. High specific activity [&lt;sup&gt;11&lt;/sup&gt;C]ADO was administrated to 3 rhesus monkeys, and PET scans of 120-minute duration were performed on the Focus-220 scanner. In the blood, [&lt;sup&gt;11&lt;/sup&gt;C]ADO metabolized at a fairly rapid rate, with ∼36% of the parent tracer remaining at 30 minutes postinjection. Uptake levels of [&lt;sup&gt;11&lt;/sup&gt;C]ADO in the brain were high (peak standardized uptake value of ∼3.0) and consistent with GABA&lt;sub&gt;A&lt;/sub&gt; distribution, with highest activity levels in cortical areas, intermediate levels in cerebellum and thalamus, and lowest uptake in striatal regions and amygdala. Tissue kinetics was fast, with peak uptake in all brain regions within 20 minutes of tracer injection. The one-tissue compartment model provided good fits to regional time-activity curves and reliable measurement of kinetic parameters. The absolute test-retest variability of regional distribution volumes ( V&lt;sub&gt;T&lt;/sub&gt;) was low, ranging from 4.5% to 8.7%. Pretreatment with flumazenil (a subtype nonselective ligand, 0.2 mg/kg, intravenous [IV], n = 1), Ro15-4513 (an α&lt;sub&gt;5&lt;/sub&gt;-selective ligand, 0.03 mg/kg, IV, n = 2), and zolpidem (an α&lt;sub&gt;1&lt;/sub&gt;-selective ligand, 1.7 mg/kg, IV, n = 1) led to blockade of [&lt;sup&gt;11&lt;/sup&gt;C]ADO binding by 96.5%, 52.5%, and 76.5%, respectively, indicating the in vivo binding specificity of the radiotracer. Using the nondisplaceable volume of distribution ( V&lt;sub&gt;ND&lt;/sub&gt;) determined from the blocking studies, specific binding signals, as measured by values of regional binding potential ( BP&lt;sub&gt;ND&lt;/sub&gt;), ranged from 0.6 to 4.4, which are comparable to those of [&lt;sup&gt;11&lt;/sup&gt;C]flumazenil. In conclusion, [&lt;sup&gt;11&lt;/sup&gt;C]ADO was demonstrated to be a specific radiotracer for the GABA&lt;sub&gt;A&lt;/sub&gt; receptors with several favorable properties: high brain uptake, fast tissue kinetics, and high levels of specific binding","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"16 ","pages":"1536012117731258"},"PeriodicalIF":2.8,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012117731258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35426838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Longitudinal Evaluation of Myocardial Fatty Acid and Glucose Metabolism in Fasted and Nonfasted Spontaneously Hypertensive Rats Using MicroPET/CT. 利用微pet /CT纵向评价空腹和非空腹自发性高血压大鼠心肌脂肪酸和葡萄糖代谢。
IF 2.8 4区 医学
Molecular Imaging Pub Date : 2017-01-01 DOI: 10.1177/1536012117724558
Jennifer S Huber, Andrew M Hernandez, Mustafa Janabi, James P O'Neil, Kathleen M Brennan, Stephanie T Murphy, Youngho Seo, Grant T Gullberg
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引用次数: 6
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