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Find video protocols related to scientific articles indexed in Pubmed.
Comparison of [(11)C]Choline ([ (11)C]CHO) and S(+)-?-Methyl-[ (11)C]Choline ([ (11)C]SMC) as Imaging Probes for Prostate Cancer in a PC-3 Prostate Cancer Xenograft Model.
Mol Imaging Biol
PUBLISHED: 08-28-2014
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Carbon-11- and fluorine-18-labeled choline derivatives have been introduced as promising tracers for prostate cancer imaging. However, due to limited specificity and sensitivity, there is a need for new tracers with higher sensitivity and specificity for diagnosing prostate cancer to improve tracer uptake and enhance imaging contrast. The aim of this study was to compare the properties of [(11)C]choline ([(11)C]CHO) with S(+)-?-methyl-[(11)C]choline ([(11)C]SMC) as tracer for prostate cancer imaging in a human prostate tumor mouse xenograft model by small-animal positron emission tomography/X-ray computed tomography (PET/CT).
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Synthesis and evaluation of three structurally related ¹?F-labeled orvinols of different intrinsic activities: 6-O-[¹?F]fluoroethyl-diprenorphine ([¹?F]FDPN), 6-O-[¹?F]fluoroethyl-buprenorphine ([¹?F]FBPN), and 6-O-[¹?F]fluoroethyl-phenethyl-orvinol ([¹?F]FPEO).
J. Med. Chem.
PUBLISHED: 06-16-2014
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We report the synthesis and biological evaluation of a triplet of 6-O-(18)F-fluoroethylated derivatives of structurally related orvinols that span across the full range of intrinsic activities, the antagonist diprenorphine, the partial agonist buprenorphine, and the full agonist phenethyl-orvinol. [(18)F]fluoroethyl-diprenorphine, [(18)F]fluoroethyl-buprenorphine, and [(18)F]fluoroethyl-phenethyl-orvinol were prepared in high yields and quality from their 6-O-desmethyl-precursors. The results indicate suitable properties of the three 6-O-(18)F-fluoroethylated derivatives as functional analogues to the native carbon-11 labeled versions with similar pharmacological properties.
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A fully automated radiosynthesis of [18F]fluoroethyl-diprenorphine on a single module by use of SPE cartridges for preparation of high quality 2-[18F]fluoroethyl tosylate.
Molecules
PUBLISHED: 05-01-2013
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We have developed a new method for automated production of 2-[18F]fluoroethyl tosylate ([18F]FETos) that enables 18F-alkylation to provide PET tracers with high chemical purity. The method is based on the removal of excess ethylene glycol bistosylate precursor by precipitation and subsequent filtration and purification of the filtrate by means of solid phase extraction cartridges (SPE). The method is integrated to a single synthesis module and thereby provides the advantage over previous methods of not requiring HPLC purification, as demonstrated by the full radiosynthesis of the potent opioid receptor PET tracer [18F]fluoroethyldiprenorphine.
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Voxel-based analysis of amyloid-burden measured with [(11)C]PiB PET in a double transgenic mouse model of Alzheimers disease.
Mol Imaging Biol
PUBLISHED: 04-11-2013
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The purpose of this study is to validate the feasibility of a voxel-based analysis of in vivo amyloid-? positron emission tomography (PET) imaging studies in transgenic mouse models of Alzheimers disease.
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Comparison of cyclic RGD peptides for ?v?3 integrin detection in a rat model of myocardial infarction.
EJNMMI Res
PUBLISHED: 03-08-2013
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Expression of ?v?3 integrin is increased after myocardial infarction as part of the repair process. Increased expression of ?v?3 has been shown by molecular imaging with 18F-galacto-RGD in a rat model. The 68Ga-labelled RGD compounds 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 have high specificity and affinity, and may therefore serve as alternatives of 18F-galacto-RGD for integrin imaging.
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Synthesis and evaluation of 18F-FE-PEO in rodents: an 18F-labeled full agonist for opioid receptor imaging.
J. Nucl. Med.
PUBLISHED: 01-07-2013
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We have investigated the opioid receptor (OR) agonist (20R)-4,5-?-epoxy-6-(2-(18)F-fluoroethoxy)-3-hydroxy-?,17-dimethyl-?-(2-phenyleth-1-yl)-6,14-ethenomorphinan-7-methanol ((18)F-FE-PEO) as a candidate OR PET ligand. This tracer is attractive because it combines (18)F labeling, is suited to the slow kinetics of high-affinity ligands, and has agonist binding, which has been shown to be more sensitive to changes in OR occupation than is antagonist binding.
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Regional expansion of hypometabolism in Alzheimers disease follows amyloid deposition with temporal delay.
Biol. Psychiatry
PUBLISHED: 03-26-2011
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Cross-sectional imaging studies suggest that patterns of hypometabolism (measured by [(18)F] fluorodeoxyglucose positron emission tomography [FDG-PET]) and amyloid deposition (measured by [(11)C] Pittsburgh Compound B [PiB]- PET) in Alzheimers disease (AD) show some overlap with each other. This indicates that neuronal dysfunction might spread within the anatomical pattern of amyloid deposition. The aim of this study was to examine longitudinal regional patterns of amyloid deposition and hypometabolism in the same population of mild AD subjects and to establish their regional relationship to each other.
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Synthesis and evaluation of 11C-labeled imidazo[2,1-b]benzothiazoles (IBTs) as PET tracers for imaging ?-amyloid plaques in Alzheimers disease.
J. Med. Chem.
PUBLISHED: 01-28-2011
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We report a novel series of (11)C-labeled imidazo[2,1-b]benzothiazoles (IBTs) as tracers for imaging of cerebral ?-amyloid (A?) deposits in patients with Alzheimers disease (AD) by means of positron emission tomography (PET). From a series of 11 compounds, candidates were identified to have a high binding affinity for A?. Selected compounds were prepared as O- or N-[(11)C]methyl derivatives and shown to have a high initial brain uptake in wild-type mice (range 1.9-9.2% I.D./g at 5 min). 2-(p-[(11)C]Methylaminophenyl)-7-methoxyimidazo[2,1-b] benzothiazole ([(11)C]5) was identified as a lead based on the combined favorable properties of high initial brain uptake, rapid clearance from normal brain, and high in vitro affinity for A?(1-40) (K(i) = 3.5 nM) and A?(1-42) (5.8 nM), which were superior to the Pittsburgh compound B (1a). In an APP/PS1 mouse model of AD (Tg), we demonstrate a specific uptake of [(11)C]5 in A?-containing telencephalic brain regions by means of small-animal PET that was confirmed by regional brain biodistribution, ex vivo autoradiography, and immunohistochemistry. Analysis of brain sections of Tg mice receiving a single bolus injection of [(11)C]5 and [(3)H]1a together revealed that the tracers bind to A? plaques in the brain of Tg mice in a comparable pattern. Taken together, these data suggest that IBTs represent useful PET imaging agents for high-sensitivity detection of A? plaques.
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Spinal long-term potentiation is associated with reduced opioid neurotransmission in the rat brain.
Clin Physiol Funct Imaging
PUBLISHED: 07-29-2010
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Neuronal events leading to development of long-term potentiation (LTP) in the nociceptive pathways may be a cellular mechanism underlying hyperalgesia. In the present study, we examine if induction of spinal LTP may be associated with functional changes in the supraspinal opioidergic system. The opioid receptors (ORs) play a key role in nociceptive processing and controlling the descending modulatory system to the spinal cord.
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Progression of cerebral amyloid load is associated with the apolipoprotein E ?4 genotype in Alzheimers disease.
Biol. Psychiatry
PUBLISHED: 01-28-2010
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Pittsburgh Compound B ([¹¹C] PiB) is a specific positron emission tomography (PET) marker of cerebral amyloid deposits. Only few data have been published on in vivo longitudinal changes of amyloid load in Alzheimers disease (AD) patients, with conflicting results. Therefore, little is known about the factors that influence these changes.
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Evaluation of the kappa-opioid receptor-selective tracer [(11)C]GR103545 in awake rhesus macaques.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 01-05-2010
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The recent development in radiosynthesis of the (11)C-carbamate function increases the potential of [(11)C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (kappa-OR) with PET. In the present study, [(11)C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound.
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Synthesis and evaluation of a full-agonist orvinol for PET-imaging of opioid receptors: [11C]PEO.
J. Med. Chem.
PUBLISHED: 08-22-2009
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Antagonist radiotracers have shown only a low sensitivity for detecting competition from high-efficacy agonists at opioid receptors (ORs) in vivo. We report that [(11)C]PEO binds with high affinity to mu and kappa-opioid receptors, is a full agonist, and concentrates in brain regions of rats with a high density of the mu-OR after intravenous injection. Blocking studies with mu and kappa-OR selective compounds demonstrated that the binding of [(11)C]PEO is saturable and selective to the mu-OR in rat brain.
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Fast and repetitive in-capillary production of [18F]FDG.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 08-14-2009
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The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 microm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [(18)F]FDG was evaluated.
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Clinical severity of Alzheimers disease is associated with PIB uptake in PET.
Neurobiol. Aging
PUBLISHED: 06-24-2009
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The positron emission tomography (PET) tracer [11C]-Pittsburgh Compound-B ([11C]PIB) allows the in vivo assessment of amyloid plaque burden in the brain. In a cross-sectional study we examined the association between the severity of dementia assessed using the Clinical Dementia Rating scale sum of boxes (CDR-SOB) and [11C]PIB-PET in patients with Alzheimers disease (AD).
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Peripheral and central biodistribution of (111)In-labeled anti-beta-amyloid autoantibodies in a transgenic mouse model of Alzheimers disease.
Neurosci. Lett.
PUBLISHED: 04-28-2009
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Active as well as passive immunization against beta-amlyoid (Abeta) has been proposed as a treatment to lower cerebral amyloid burden and stabilize cognitive decline in Alzheimers disease (AD). To clarify the mechanism of action underlying passive immunization, the in vivo distribution (and sites of degradation) of peripherally administered radiolabeled human and mouse anti-Abeta antibodies were analyzed in a transgenic mouse model of AD. In APP23 mice, a model in which mutated human amyloid precursor protein is overexpressed, the biodistribution of intravenously applicated (111)indium-conjugated affinity-purified human polyclonal autoantibodies (NAbs-Abeta) was compared to that of monoclonal anti-Abeta(1-17) (6E10), anti-Abeta(17-24) antibodies (4G8) and anti-CD-20 (Rituximab), a non-Abeta targeting control. Blood clearance half-lives were 50+/-6h for Rituximab, 20-30h for NAbs-Abeta, 29+/-5h for 4G8 and 27+/-3h for 6E10. Blood activity was higher for 6E10 at 4h as compared to 4G8, Rituximab and NAbs-Abeta. At the 96h time point, Rituximab had the highest blood activity among the antibodies tested. As expected, all antibodies displayed hepatobiliary clearance. Additionally, NAbs-Abeta was excreted in the urinary tract. Liver and kidney uptake of NAbs-Abeta increased over time and was higher than in the monoclonal antibodies at 48h/96h. The brain-to-blood radioactivity ratio for NAbs-Abeta at later time points (>48h) was higher than that of 6E10, 4G8 and Rituximab. In addition, the distribution varied, with highest values found in the hippocampus. Our data indicate a cerebral accumulation of human NAbs-Abeta in the APP23 model. Further studies with human immunoglobulins and particularly with those that recognize different Abeta-epitopes are required in order to delineate in more detail the mode of action of NAbs-Abeta.
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Early-onset and robust amyloid pathology in a new homozygous mouse model of Alzheimers disease.
PLoS ONE
PUBLISHED: 04-22-2009
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Transgenic mice expressing mutated amyloid precursor protein (APP) and presenilin (PS)-1 or -2 have been successfully used to model cerebral beta-amyloidosis, one of the characteristic hallmarks of Alzheimers disease (AD) pathology. However, the use of many transgenic lines is limited by premature death, low breeding efficiencies and late onset and high inter-animal variability of the pathology, creating a need for improved animal models. Here we describe the detailed characterization of a new homozygous double-transgenic mouse line that addresses most of these issues.
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Evaluation of a novel (18)F-labeled positron-emission tomography perfusion tracer for the assessment of myocardial infarct size in rats.
Circ Cardiovasc Imaging
PUBLISHED: 01-26-2009
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The goal of this study was to evaluate a new (18)F-labeled positron-emission tomography (PET) perfusion tracer, (18)F BMS747158-02, for the assessment of myocardial infarct (MI) size.
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Beta amyloid in Alzheimers disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid.
Biol. Psychiatry
PUBLISHED: 01-08-2009
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A decreased concentration of beta amyloid (1-42) (Abeta42) has consistently been found in the cerebrospinal fluid (CSF) of patients with Alzheimers disease (AD) and is considered a diagnostic biomarker. However, it is not clear to which extent CSF Abeta42 levels are reflective of cerebral pathology in AD. The aim of the study was to determine the association between cerebral amyloid plaque load, as measured by means of the positron emission tomography (PET) tracer carbon-11-labeled Pittsburgh Compound B ([11C]PiB) and CSF Abeta42 in AD.
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Design and synthesis of an ¹?F-labeled version of phenylethyl orvinol ([¹?F]FE-PEO) for PET-imaging of opioid receptors.
Molecules
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The semisynthetic oripavine derivative phenethyl orvinol (PEO), a full agonist at opioid receptors (OR), is an attractive structural motif for developing ¹?F-labeled PET tracers with a high degree of sensitivity for competition between endogenous and exogenous OR-ligands. The target cold reference compound 6-O-(2-fluoroethyl)-6-O-desmethylphenylethyl orvinol (FE-PEO) was obtained via two separate reaction routes. A three-step synthesis was developed for the preparation of a tosyloxyethyl precursor (TE-TDPEO), the key precursor for a direct, nucleophilic radiofluorination to yield [¹?F]FE-PEO. The developed radiosynthesis provides the target compound in relevantly high yield and purity, and is adaptable to routine production.
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Small-animal PET imaging of amyloid-beta plaques with [11C]PiB and its multi-modal validation in an APP/PS1 mouse model of Alzheimers disease.
PLoS ONE
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In vivo imaging and quantification of amyloid-? plaque (A?) burden in small-animal models of Alzheimers disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of A? in mouse brain with [(11)C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure A? at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [(11)C]PiB uptake in individual brain regions with A? deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of A? pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [(11)C]PiB imaging of A? in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal A? imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice.
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White matter hyperintensities predict amyloid increase in Alzheimers disease.
Neurobiol. Aging
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Impaired amyloid clearance probably contributes to increased amyloid deposition in sporadic Alzheimers disease (AD). Diminished perivascular drainage due to cerebral small-vessel disease (CSVD) has been proposed as a cause of reduced amyloid clearance. White matter hyperintensities (WMHs) are considered to reflect CSVD and can be measured using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Amyloid deposition can be determined in vivo using Pittsburgh compound B ([11C]PiB) positron emission tomography (PET). We aimed to elucidate the association between WMH and the progression of amyloid deposition in patients with AD. Twenty-two patients with probable AD underwent FLAIR-MRI and [11C]PiB-PET examinations at baseline (BL) and after a mean follow-up (FU) interval of 28 months. The relationship between BL-WMH and the progression of cerebral amyloid between BL and FU was examined using a regions-of-interest (ROI) approach. The region-specific variability of this relationship was analyzed using a voxel-based method. The longitudinal analysis revealed a statistically significant association between the amount of BL-WMH and the progression of amyloid load between BL and FU (p = 0.006, adjusted R2 = 0.375, standardized coefficient ? = 0.384). The association was particularly observed in parieto-occipital regions and tended to be closer in regions adjacent to the brain surface. According to our knowledge, this is the first in vivo study in human being supporting the hypothesis that impaired amyloid clearance along perivascular drainage pathways may contribute to ?-amyloid deposition in sporadic AD. The extent of WMH might be a relevant factor to be assessed in antiamyloid drug trials.
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A convenient route to 4-carboxy-4-anilidopiperidine esters and acids.
Molecules
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The route selection and development of a convenient synthesis of 4-carboxy-4-anilidopiperidines is described. Previous routes were hampered by the low yield of the target esters as well as the inability to convert the esters to the required free acids. Considerations for large-scale production led to a modified synthesis that utilised a tert-butyl ester of 4-carboxy-4-anilidopiperidines which resulted in a dramatic increase in the overall yield of the target N-propionylated- 4-anilidopiperidine-4-carboxylic acids and their corresponding methyl esters. These compounds are now available for use as precursors and reference standards, of particular value for the production of 11C and 18F-labelled 4-carboxy-4-anilidopiperidine radiotracers.
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Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimers disease.
ScientificWorldJournal
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The secretase BACE1 is fundamentally involved in the development of cerebral amyloid pathology in Alzheimers disease (AD). It has not been studied so far to what extent BACE1 activity in cerebrospinal fluid (CSF) mirrors in vivo amyloid load in AD. We explored associations between CSF BACE1 activity and fibrillar amyloid pathology as measured by carbon-11-labelled Pittsburgh Compound B positron emission tomography ([¹¹C]PIB PET). [¹¹C]PIB and CSF studies were performed in 31 patients with AD. Voxel-based linear regression analysis revealed significant associations between CSF BACE1 activity and [¹¹C]PIB tracer uptake in the bilateral parahippocampal region, the thalamus, and the pons. Our study provides evidence for a brain region-specific correlation between CSF BACE1 activity and in-vivo fibrillar amyloid pathology in AD. Associations were found in areas close to the brain ventricles, which may have important implications for the use of BACE1 in CSF as a marker for AD pathology and for antiamyloid treatment monitoring.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.