The overarching aim is to assess the role of microglial activation and norepinephrine transporter binding in pathogenesis of MS-related fatigue, using novel Positron Emission Tomography (PET) radiotracers, [F-18]PBR06 and [C-11]MRB.
Specific Aims:
Specific Aim 1: To determine the relationship of cerebral microglial activation, as assessed by [F-18]PBR06 PET, with MS-related fatigue.
Specific Aim 2: To determine the relationship of norepinephrine transporter (NET) binding, as assessed by [C-11]MRB PET, with MS-related fatigue.
Specific Aim 3: To determine the relationship of microglial activation and NET binding, with grey matter pathology (lesion load and brain atrophy) assessed using 7T MRI, and evaluate their independent contribution in development of MS-related fatigue.

开始日期2020-03-12

申办/合作机构

The Brigham & Women's Hospital, Inc.

NCT03648905 / Active, not recruitingN/AIIT

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Background:
The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure.
Objective:
To improve testing for conditions that cause autonomic nervous system failure.
Eligibility:
People ages 18 and older in one of these categories:
* Their blood pressure drops when they get up.
* They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation
Design:
All participants will be screened with:
* Medical history
* Physical exam
* Blood and urine tests
Some participants will be screened with:
* Heart and breathing tests
* IV placement into an arm vein
* Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood.
Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and:
* Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture.
* Lumbar puncture: A needle is inserted between the bones in the back to collect fluid.
* MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical.
* Bladder catheter placement to collect urine
* Skin biopsies: A punch tool removes a small skin sample.
* Tests to see how the pupils react to light
* Smelling tests
* Thinking and memory tests
* Questionnaires
Participants may have a visit about 2 years later to repeat tests.

开始日期2018-09-06

申办/合作机构

National Institute of Neurological Disorders & Stroke

NCT03207464 / Unknown status临床1/2期IIT

Molecular Imaging of Norepinephrine Transporter (NET) Using [C-11]Methylreboxetine PET in Multiple Sclerosis

This study aims to use [C-11]MRB PET (positron emission tomography) imaging to look at brain injury in patients with Multiple Sclerosis (MS) and healthy individuals. The overarching hypothesis is that there is decreased radioligand binding to the norepinephrine transporter in multiple sclerosis, reflecting injury to the noradrenergic system and that it plays a role in disease pathogenesis, its clinical manifestations and severity. This strategy is targeted to address an unmet need because currently available MRI techniques lack sensitivity and specificity for assessing such changes in the brains of people with MS.
The specific aims of the study are:
To determine norepinephrine transporter binding in the brains of MS patients using [C-11]MRB PET and compare it with age, and sex matched healthy controls.
To determine correlation of norepinephrine transporter binding with clinical severity and MRI parameters in MS.
To determine correlation of norepinephrine transporter binding with fatigue and cognitive impairment in MS patients.

开始日期2017-10-10

申办/合作机构

The Brigham & Women's Hospital, Inc.

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100 项与 (S,S)-[11C]Mener 相关的转化医学

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项与 (S,S)-[11C]Mener 相关的文献（医药）

2019-12-01·EJNMMI Research3区 · 医学

PET imaging of hepatocellular carcinoma with anti-1-amino-3-[18F]fluorocyclobutanecarboxylic acid in comparison with l-[S-methyl-11C]methionine

3区 · 医学

ArticleOA

作者: Kenyon, Jonathan D ; Xin, Wei ; Wojtylak, Patrick ; Iyer, Renuka ; Zhang, Yifan ; Lee, Zhenghong ; Chan, E Ricky ; Sergeeva, Olga ; Miller-Atkins, Galen A ; Wu, Chunying ; Awadallah, Amad ; Sexton, Sandra ; O'Donnel, James K

PURPOSE[¹¹C]methionine ([¹¹C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of ¹¹C decay limited further clinical development of [¹¹C]Met. Synthetic amino acid analog anti-1-amino-3-[¹⁸F]fluoro-cyclobutyl-1-carboxylic acid ([¹⁸F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer. This study investigated "repurposed" [¹⁸F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [¹¹C]Met.METHODS[¹¹C]Met was synthesized in the lab, and [¹⁸F]FACBC was purchased from a commercial outlet. A clinically relevant animal model of spontaneously developed HCC in the woodchucks was used for PET imaging. Bioinformatics analysis was performed for the expression of amino acid transporters responsible for radiotracer uptake and validated by PCR. Dynamic PET scans of [¹¹C]Met and [¹⁸F]FACBC were acquired within 1 week. Standardized uptake value (SUV) was calculated for regions of interest (ROIs) defined over HCC and a liver background region. H&E staining and immunohistochemical (IHC) staining were performed with harvested tissues post-imaging.RESULTSHigher expression of ACST2 and LAT1 was found in HCC than in the surrounding liver tissues. PCR validated this differential expression. [¹¹C]Met and [¹⁸F]FACBC displayed some differences in their uptake and retention in HCC. Both peaked in HCC with an SUV of 3.5 after 10 min post-injection. Met maintained a plateaued contrast uptake in HCC to that in the liver while [¹⁸F]FCABC declined in HCC and liver after peak uptake. The pathological assessment revealed the liver tumor as moderately differentiated similar to the human HCC and proliferative.CONCLUSIONBoth [¹⁸F]FACBC and [¹¹C]Met showed uptake in HCC through the use of a clinically relevant animal model of woodchuck HCC. The uptake and retention of [¹⁸F]FACBC and [¹¹C]Met depend on their metabolism and also rely on the distribution of their principal amino acid transporters.

2019-01-02·Stress3区 · 心理学

Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls

3区 · 心理学

Article

作者: Schmidt, Elisa ; Schinke, Christian ; Rullmann, Michael ; Orthgieß, Johannes ; Meyer, Philipp M. ; Sabri, Osama ; Becker, Georg-Alexander ; Blüher, Matthias ; Ding, Yu-Shin ; Hesse, Swen ; Meyer, Klara ; Stoppe, Muriel ; Kratzsch, Jürgen ; Zientek, Franziska ; Patt, Marianne ; Then Bergh, Florian ; Luthardt, Julia

The central noradrenaline (NA) stress-response network co-mediates hypothalamic-pituitary-adrenal (HPA) axis activation and arginine-vasopressin (AVP) release. Dysregulation of these systems contributes to stress-related diseases such as human obesity, but their interrelation remains unclear. The study was aimed to test for the first time in vivo whether central noradrenergic activity quantitatively indexed by the availability of the presynaptic NA transporter (NAT) is associated with HPA axis responsiveness as measured with the combined dexamethasone suppression/corticotropin releasing hormone stimulation (dex/CRH) test and copeptin as a surrogate marker of the serum AVP tone in highly obese, otherwise, healthy individuals compared to age- and sex-matched non-obese, healthy controls. In order to assess central NAT availability, positron emission tomography (PET) was applied using the NAT-selective radiotracer S,S-[¹¹C]O-methylreboxetine (MRB) and correlated with curve indicators derived from the dex/CRH test (maximum, MAX, and area under the curve, AUC, for cortisol and adrenocorticotropic hormone, ACTH) as well as with copeptin. In non-obese controls, positive correlations were found between the NAT distribution volume ratios (DVR) of the orbitofrontal cortex (OFC) and the amygdala with the HPA response (OFC: ACTH_MAX r = 0.87, p = .001; cortisol_MAX r = 0.86, p = .002; amygdala: ACTH_MAX r = 0.86, p = .002; cortisol_MAX r = 0.79, p = .006), while in obesity, the hypothalamic DVR correlated inversely with the HPA axis response (cortisol_MAX, r = -0.66, p = .04) and with copeptin (r = -0.71, p = .02). This association of central NAT availability with HPA axis responsiveness and copeptin suggests a mechanistic interaction between noradrenergic transmission with HPA axis activity and the serum AVP system that differs between non-obese individuals with prefrontal-limbic involvement and obesity with a hypothalamic-centered relationship. Whether the latter finding contributes to obesogenic behavior needs to be further explored.

2018-06-01·Molecular Imaging and Biology3区 · 医学

PET Imaging with S-[11C]Methyl-L-Cysteine and L-[Methyl-11C]Methionine in Rat Models of Glioma, Glioma Radiotherapy, and Neuroinflammation

3区 · 医学

Article

作者: Doorduin, Janine ; Maas, Bram ; Parente, Andrea ; de Vries, Erik F J ; van Waarde, Aren ; de Paula Faria, Daniele ; Shoji, Alexandre ; Dierckx, Rudi A J O ; Langendijk, Johannes A ; Zijlma, Rolf

PURPOSES-[¹¹C]-methyl-L-cysteine ([¹¹C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- ¹¹C]methionine ([¹¹C]MET). We examined this claim in animal models.PROCEDURESRats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days.RESULTSUptake of the two tracers in untreated gliomas was similar. [¹¹C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [¹¹C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [¹¹C]MCYS indicated higher lesion volumes than [¹¹C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %).CONCLUSIONS[¹¹C]MCYS was less accumulated in some non-tumor tissues than [¹¹C]MET, but showed lower tumor-to-brain contrast.

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适应症	最高研发状态	国家/地区	公司	日期
多发性硬化症	临床2期	-	The Brigham & Women's Hospital, Inc.	-
多发性硬化症	临床2期	-	The Trustees of Columbia University in The City of New York	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AAIC2020	N/A	-	31	[11C]MRB (All HC)	壓襯艱顧壓鑰襯願餘顧(鹹醖顧鹽醖築醖繭顧淵) = 夢遞鹹獵簾積餘衊遞廠遞願繭淵觸淵簾製觸醖 (蓋繭鹹顧膚簾窪範鬱齋 )	-	2020-12-07
				[11C]MRB (Male HC)	壓襯艱顧壓鑰襯願餘顧(鹹醖顧鹽醖築醖繭顧淵) = 廠窪夢壓廠齋鬱網鹽衊遞願繭淵觸淵簾製觸醖 (蓋繭鹹顧膚簾窪範鬱齋 )
SNMMI2020	N/A	胃肠胰神经内分泌肿瘤	-	[ 11 C]MRB (Male)	膚鬱艱願齋選糧醖選糧(壓獵鏇築鹹鹽壓繭壓糧) = 憲顧鏇鑰廠襯糧鏇遞艱製壓夢壓餘鑰構簾淵選 (鬱憲遞壓製鹽憲淵選膚 ) 更多	-	2020-05-15
				[ 11 C]MRB (Female)	膚鬱艱願齋選糧醖選糧(壓獵鏇築鹹鹽壓繭壓糧) = 衊獵鏇醖鑰獵醖蓋夢顧製壓夢壓餘鑰構簾淵選 (鬱憲遞壓製鹽憲淵選膚 ) 更多