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Find video protocols related to scientific articles indexed in Pubmed.
A bioorthogonal (68)Ga-labelling strategy for rapid in vivo imaging.
Chem. Commun. (Camb.)
PUBLISHED: 07-12-2014
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Herein, we describe a fast and robust method for achieving (68)Ga-labelling of the EGFR-selective monoclonal antibody (mAb) Cetuximab using the bioorthogonal Inverse-electron-Demand Diels-Alder (IeDDA) reaction. The in vivo imaging of EGFR is demonstrated, as well as the translation of the method within a two-step pretargeting strategy.
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A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography.
Cancer Res.
PUBLISHED: 03-05-2014
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The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that (18)F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3]triazole-4-yl)glucosamine ((18)F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating (18)F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited (18)F-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, (18)F-NFTG, but not (18)F-FDG uptake, increase proportionally with cell density and G1-G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence.
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Biodistribution and radiation dosimetry of deuterium-substituted 18F-fluoromethyl-[1, 2-2H4]choline in healthy volunteers.
J. Nucl. Med.
PUBLISHED: 02-05-2014
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(11)C-choline and (18)F-fluoromethylcholine ((18)F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, (18)F-fluoromethyl-[1,2-(2)H4]choline ((18)F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of (18)F-D4-FCH in 8 healthy human volunteers.
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Radiolabeled RGD Tracer Kinetics Annotates Differential ?v? 3 Integrin Expression Linked to Cell Intrinsic and Vessel Expression.
Mol Imaging Biol
PUBLISHED: 09-12-2013
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The purpose of this paper is to study the association between RGD binding kinetics and ?v?3 integrin receptor density in the complex tumor milieu.
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Bioorthogonal chemistry for pre-targeted molecular imaging--progress and prospects.
Org. Biomol. Chem.
PUBLISHED: 08-03-2013
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The aim of this perspective is to critically review the three most prominent bioorthogonal reactions that are used presently, on both a purely chemical level and in the context of biological systems. This includes the uses both for synthesis of therapeutic molecules, modification of large biomolecules or antibodies, and in particular, the exciting use in the field of pre-targeting, for both possible treatment and imaging technologies. We will compare the validity of each reaction when compared to others, and their usefulness in biological systems, as each methodology has clear advantages over the others in differing environments.
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Bioorthogonal chemistry for (68) Ga radiolabelling of DOTA-containing compounds.
J Labelled Comp Radiopharm
PUBLISHED: 06-04-2013
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Copper-catalysed click chemistry is a highly utilised technique for radiolabelling small molecules and peptides for imaging applications. The usefulness of these reactions falls short, however, when metal catalysis is not a practically viable route; such as when using metal chelates as radioligands. Here, we describe a method for carrying out click-type radiochemistry in the presence of DOTA chelates, by combining (68) Ga radiolabelling techniques with well-established bioorthogonal reactions, which do not rely upon metal catalysis.
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Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging.
Clin. Cancer Res.
PUBLISHED: 05-31-2013
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Induction of apoptosis in tumors is considered a desired goal of anticancer therapy. We investigated whether the dynamic temporal and spatial evolution of apoptosis in response to cytotoxic and mechanism-based therapeutics could be detected noninvasively by the caspase-3 radiotracer [(18)F]ICMT-11 and positron emission tomography (PET).
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Copper-free click--a promising tool for pre-targeted PET imaging.
Chem. Commun. (Camb.)
PUBLISHED: 12-07-2011
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The copper-free click (CFC) reaction has been evaluated for its potential application to in vivo pre-targeting for PET imaging. A promising biodistribution profile is demonstrated when employing [(18)F]2-fluoroethylazide ([(18)F]1) and optimisation of the CFC reaction with a series of cyclooctynes shows that reactions proceed efficiently with tantalizing opportunities for application-specific tuning.
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A fluorous and click approach for screening potential PET probes: Evaluation of potential hypoxia biomarkers.
Bioorg. Med. Chem.
PUBLISHED: 09-09-2011
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Radiopharmaceuticals for nuclear imaging are essentially targeting molecules, labeled with short-lived radionuclides (e.g., F-18 for PET). A significant drawback of radiopharmaceuticals development is the difficulty to access radiolabeled molecule libraries for initial in vitro evaluation, as radiolabeling has to be optimized for each individual molecule. The present paper discloses a method for preparing libraries of (18)F-labeled radiopharmaceuticals using both the fluorous-based (18)F-radiochemistry and the Huisgen 1,3-dipolar (click) conjugation reaction. As a proof of concept, this approach allowed us to obtain a series of readily accessible (18)F-radiolabeled nitroaromatic molecules, for exploring their structure-activity relationship and further in vitro evaluation of their hypoxic selectivity.
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The traceless Staudinger ligation for indirect 18F-radiolabelling.
Org. Biomol. Chem.
PUBLISHED: 11-22-2010
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The Staudinger ligation of phosphine-substituted thioesters with (18)F-fluoroethylazide has been successfully applied to access (18)F-labelled molecules in radiochemical yields superior to 95%; the first fluorous variant of a Staudinger radio-ligation has been validated.
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Orthogonal 18F and 64Cu labelling of functionalised bis(thiosemicarbazonato) complexes.
Chem. Commun. (Camb.)
PUBLISHED: 04-20-2010
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The synthesis of three pairs of orthogonally labelled fluorinated Cu bis(thiosemicarbazonato) complexes is presented. These are the first examples of (18)F-labelled Cu(II)-complexes designed to serve as new hypoxia selective PET tracers and as mechanistic probes to study the mode of action of this class of markers. In vitro evaluation revealed that the fluorinated Cu-complex derived from amide coupling is suitable for in vivo work.
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Pre-clinical evaluation of a 3-nitro-1,2,4-triazole analogue of [18F]FMISO as hypoxia-selective tracer for PET.
Nucl. Med. Biol.
PUBLISHED: 02-24-2010
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Hypoxia in solid tumours is associated with the promotion of various metabolic mechanisms and induces resistance to radio- and chemotherapy. Non-invasive positron emission tomography (PET) or single photon emission computed tomography by use of selective biomarkers has emerged as valuable tools for the detection of hypoxic areas within tumours so treatment can be modified accordingly. The aim of this investigation was to evaluate [(18)F]3-NTR, a 3-nitro-1,2,4-triazole analogue (N(1) substituted) of [(18)F]FMISO as a potential hypoxia selective tracer. 3-NTR and its (18)F-radiolabelled isotopic isomer were synthesised and compared with FMISO in vitro and in vivo. Their physicochemical properties were measured, the enzymatic reduction was evaluated, and the reactivity of their metabolites was investigated. Biodistribution and PET scans were performed on CBA mice bearing hypoxic CaNT tumour cells, using (18)F-labelled versions of the tracers. [(18)F]3-NTR uptake within hypoxic cells was lower than [(18)F]FMISO and [(18)F]3-NTR did not exhibit any better selectivity than FMISO as a PET tracer in vivo. Both (18)F-radiolabelled compounds are relatively evenly distributed within the whole body and the radioactive uptake within hypoxic tumours reaches a maximum at 30 min post injection and decreases thereafter. Xanthine oxidase exhibited a nitroreductase activity toward 3-NTR under anaerobic conditions, but reduced metabolites did not bind covalently. It is confirmed that 3-NTR is an electron acceptor. It is postulated that radiolabelled metabolites and fragments of [(18)F]3-NTR are freely diffusing due to their poor binding capacities. Thus [(18)F]3-NTR cannot be used as a hypoxia selective tracer for PET. The investigation provides insights into the importance of the propensity to form covalent adducts for such biomarkers.
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New frontiers in the design and synthesis of imaging probes for PET oncology: current challenges and future directions.
Mol Imaging Biol
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Despite being developed over 30 years ago, 2-deoxy-2-[(18)F]fluoro-D-glucose remains the most frequently used radiotracer in PET oncology. In the last decade, interest in new and more specific radiotracers for imaging biological processes of oncologic interest has increased exponentially. This review summarizes the strategies underlying the development of those probes together with their validation and status of clinical translation; a brief summary of new radiochemistry strategies applicable to PET imaging is also included. The article finishes with a consideration of the challenges imaging scientists must overcome to bring about increased adoption of PET as a diagnostic or pharmacologic tool.
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Radiosynthesis and in vivo tumor uptake of 2-deoxy-2-[(18)F]fluoro-myo-inositol.
Bioorg. Med. Chem. Lett.
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Inositols play an important role in membrane lipid metabolism and mitogenic signaling of most cancer cells. There is paucity of data on the distribution of radiolabelled inositols. Based on work previously carried out on 1-deoxy-1-[(18)F]fluoro-scyllo-inositol ([(18)F]2), we began a program of work to label myo-inositol (2-deoxy-2-[(18)F]fluoro-myo-inositol, [(18)F]1), the most abundant inositol in cells. Fluorination of a triflate precursor 4 afforded the desired [(18)F]1 following deprotection with a radiochemical yield of 8% n.d.c. [(18)F]1 showed higher uptake in vivo in a human breast cancer xenograft model, MDA-MB-231, compared to [(18)F]2. Thus, we have developed a new inositol radiotracer that could have utility for studying inositol uptake in tumors.
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Synthesis and evaluation of nucleoside radiotracers for imaging proliferation.
Nucl. Med. Biol.
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Uncontrolled proliferation is a fundamental characteristic of cancer, and consequently, imaging of tumor proliferative status finds interest clinically both as a diagnostic tool and for evaluation of response to treatment. Positron emission tomography (PET) radiotracers based on a nucleoside core, such as 3-[18F]fluoro-3-deoxythymidine ([18F]FLT), have been extensively studied for this purpose. However, [18F]FLT suffers from poor DNA incorporation leading to occasional poor correlation of [18F]FLT tumor uptake with other proliferation indicators such as Ki-67 immunostaining.
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Evaluation of deuterated 18F- and 11C-labeled choline analogs for cancer detection by positron emission tomography.
Clin. Cancer Res.
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(11)C-Choline-positron emission tomography (PET) has been exploited to detect the aberrant choline metabolism in tumors. Radiolabeled choline uptake within the imaging time is primarily a function of transport, phosphorylation, and oxidation. Rapid choline oxidation, however, complicates interpretation of PET data. In this study, we investigated the biologic basis of the oxidation of deuterated choline analogs and assessed their specificity in human tumor xenografts.
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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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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.