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Thomas L. Mindt - One of the best experts on this subject based on the ideXlab platform.
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Radiolabelling of the octadentate chelators DFO* and oxoDFO* with zirconium-89 and gallium-68
JBIC Journal of Biological Inorganic Chemistry, 2020Co-Authors: Marie Brandt, Joseph Cowell, Margaret L. Aulsebrook, Gilles Gasser, Thomas L. MindtAbstract:In recent years, clinical imaging with zirconium-89 (^89Zr)-labelled monoclonal antibodies (Ab) by positron emission tomography (immunoPET) has been gaining significant importance in nuclear medicine for the diagnosis of different types of cancer. For complexation of the radiometal ^89Zr and its attachment to the Ab, chelating agents are required. To date, only the hexadentate chelator desferrioxamine (DFO) is applied in the clinic for this purpose. However, there is increasing preclinical evidence that the [^89Zr]Zr-DFO complex is not sufficiently stable and partly releases the radiometal in vivo due to the incomplete coordination sphere of the metal. This leads to unfavourable unspecific uptake of the osteophilic radiometal in bones, hence decreasing the signal-to-noise-ratio and leading to an increased dose to the patient. In the past, several new chelators with denticities > 6 have been published, notably the octadentate DFO derivative DFO*. DFO*, however, shows limited water solubility, wherefore an oxygen containing analogue, termed oxoDFO*, was developed in 2017. However, no data on the suitability of oxoDFO* for radiolabelling with ^89Zr has yet been reported. In this proof-of-concept study, we present the first radiolabelling results of the octadentate, water-soluble chelator oxoDFO*, as well as the in vitro stability of the resulting complex [^89Zr]Zr-oxoDFO* in comparison to the analogous octadentate, but less water-soluble derivative DFO* and the current “standard” chelator DFO. In addition, the suitability of DFO* and oxoDFO* for Radiolabeling with the short-lived PET metal gallium-68 is discussed. Graphic abstract The water-soluble, octadentate chelator oxoDFO* provides stable complexes with the positron emitter Zirconium-89. The radiolabelling can be performed at room temperature and neutral pH and thus, oxoDFO* represents a promising chelator for applications in immunoPET.
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Radiolabelling of the octadentate chelators DFO* and oxoDFO* with zirconium-89 and gallium-68
Journal of Biological Inorganic Chemistry, 2020Co-Authors: Marie Brandt, Joseph Cowell, Margaret L. Aulsebrook, Gilles Gasser, Thomas L. MindtAbstract:In recent years, clinical imaging with zirconium-89 (89Zr)-labelled monoclonal antibodies (Ab) by positron emission tomography (immunoPET) has been gaining significant importance in nuclear medicine for the diagnosis of different types of cancer. For complexation of the radiometal 89Zr and its attachment to the Ab, chelating agents are required. To date, only the hexadentate chelator desferrioxamine (DFO) is applied in the clinic for this purpose. However, there is increasing preclinical evidence that the [89Zr]Zr-DFO complex is not sufficiently stable and partly releases the radiometal in vivo due to the incomplete coordination sphere of the metal. This leads to unfavourable unspecific uptake of the osteophilic radiometal in bones, hence decreasing the signal-to-noise-ratio and leading to an increased dose to the patient. In the past, several new chelators with denticities > 6 have been published, notably the octadentate DFO derivative DFO*. DFO*, however, shows limited water solubility, wherefore an oxygen containing analogue, termed oxoDFO*, was developed in 2017. However, no data on the suitability of oxoDFO* for radiolabelling with 89Zr has yet been reported. In this proof-of-concept study, we present the first radiolabelling results of the octadentate, water-soluble chelator oxoDFO*, as well as the in vitro stability of the resulting complex [89Zr]Zr-oxoDFO* in comparison to the analogous octadentate, but less water-soluble derivative DFO* and the current “standard” chelator DFO. In addition, the suitability of DFO* and oxoDFO* for Radiolabeling with the short-lived PET metal gallium-68 is discussed.
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click to chelate development of technetium and rhenium tricarbonyl labeled radiopharmaceuticals
Molecules, 2013Co-Authors: Christiane A Kluba, Thomas L. MindtAbstract:The Click-to-Chelate approach is a highly efficient strategy for the Radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction) enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (bio)molecules with the ligand system and Radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.
Benjamin Guillet - One of the best experts on this subject based on the ideXlab platform.
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A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [ 18 F]fluoride: Will [ 18 F]AlF Replace 68 Ga for Metal Chelate Labeling?
Molecules, 2019Co-Authors: Cyril Fersing, Ahlem Bouhlel, Christophe Cantelli, Philippe Garrigue, Vincent Lisowski, Benjamin GuilletAbstract:Due to its ideal physical properties, fluorine-18 turns out to be a key radionuclide for positron emission tomography (PET) imaging, for both preclinical and clinical applications. However, usual biomolecules radiofluorination procedures require the formation of covalent bonds with fluorinated prosthetic groups. This drawback makes radiofluorination impractical for routine Radiolabeling, gallium-68 appearing to be much more convenient for the labeling of chelator-bearing PET probes. In response to this limitation, a recent expansion of the 18 F chemical toolbox gave aluminum [ 18 F]fluoride chemistry a real prominence since the late 2000s. This approach is based on the formation of an [ 18 F][AlF] 2+ cation, complexed with a 9-membered cyclic chelator such as NOTA, NODA or their analogs. Allowing a one-step radiofluorination in an aqueous medium, this technique combines fluorine-18 and non-covalent Radiolabeling with the advantage of being very easy to implement. Since its first reports, [ 18 F]AlF Radiolabeling approach has been applied to a wide variety of potential PET imaging vectors, whether of peptidic, proteic, or small molecule structure. Most of these [ 18 F]AlF-labeled tracers showed promising preclinical results and have reached the clinical evaluation stage for some of them. The aim of this report is to provide a comprehensive overview of [ 18 F]AlF labeling applications through a description of the various [ 18 F]AlF-labeled conjugates, from their radiosynthesis to their evaluation as PET imaging agents.
Brian M. Zeglis - One of the best experts on this subject based on the ideXlab platform.
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Click Chemistry and Radiochemistry: The First 10 Years
Bioconjugate Chemistry, 2016Co-Authors: Jan-philip Meyer, Pierre Adumeau, Jason S. Lewis, Brian M. ZeglisAbstract:The advent of click chemistry has had a profound influence on almost all branches of chemical science. This is particularly true of radiochemistry and the synthesis of agents for positron emission tomography (PET), single photon emission computed tomography (SPECT), and targeted radiotherapy. The selectivity, ease, rapidity, and modularity of click ligations make them nearly ideally suited for the construction of radiotracers, a process that often involves working with biomolecules in aqueous conditions with inexorably decaying radioisotopes. In the following pages, our goal is to provide a broad overview of the first 10 years of research at the intersection of click chemistry and radiochemistry. The discussion will focus on four areas that we believe underscore the critical advantages provided by click chemistry: (i) the use of prosthetic groups for Radiolabeling reactions, (ii) the creation of coordination scaffolds for radiometals, (iii) the site-specific Radiolabeling of proteins and peptides, and (iv...
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Enzyme-Mediated Methodology for the Site-Specific Radiolabeling of Antibodies Based on Catalyst-Free Click Chemistry
Bioconjugate Chemistry, 2013Co-Authors: Brian M. Zeglis, Brian J. Agnew, Aimei Chen, Hee Chol Kang, Robert Aggeler, Charles B. Davis, Jason S. LewisAbstract:An enzyme- and click chemistry-mediated methodology for the site-selective Radiolabeling of antibodies on the heavy chain glycans has been developed and validated. To this end, a model system based on the prostate specific membrane antigen-targeting antibody J591, the positron-emitting radiometal 89Zr, and the chelator desferrioxamine has been employed. The methodology consists of four steps: (1) the removal of sugars on the heavy chain region of the antibody to expose terminal N-acetylglucosamine residues; (2) the incorporation of azide-modified N-acetylgalactosamine monosaccharides into the glycans of the antibody; (3) the catalyst-free click conjugation of desferrioxamine-modified dibenzocyclooctynes to the azide-bearing sugars; and (4) the Radiolabeling of the chelator-modified antibody with 89Zr. The site-selective labeling methodology has proven facile, reproducible, and robust, producing 89Zr-labeled radioimmunoconjguates that display high stability and immunoreactivity in vitro (>95%) in addition ...
Todd E. Barnhart - One of the best experts on this subject based on the ideXlab platform.
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chelator free labeling of metal oxide nanostructures with zirconium 89 for positron emission tomography imaging
ACS Nano, 2017Co-Authors: Liang Cheng, Shreya Goel, Emily B Ehlerding, Sida Shen, Paul A Ellison, Guosheng Song, Peng Huang, Dawei Jiang, Todd E. BarnhartAbstract:Radiolabeling of molecules or nanoparticles to form imaging probes is critical for positron emission tomography (PET) imaging, which, with high sensitivity and the ability for quantitative imaging, has been widely used in the clinic. While conventional Radiolabeling often employs chelator molecules, a general method for chelator-free Radiolabeling of a wide range of materials remains to be developed. Herein, we determined that 10 different types of metal oxide (MxOy, M = Gd, Ti, Te, Eu, Ta, Er, Y, Yb, Ce, or Mo, x = 1–2, y = 2–5) nanomaterials with polyethylene glycol (PEG) modification could be labeled with 89Zr, a PET tracer, via a simple yet general chelator-free Radiolabeling method upon simple mixing. High-labeling yields and good serum stabilities are achieved with this method, owing to the strong bonding between oxyphilic 89Zr4+ with oxygen atoms on the MxOy surface. Selecting 89Zr–Gd2O3–PEG as a multimodal imaging probe, we have successfully demonstrated in vivo PET imaging of draining lymph nodes...
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intrinsic Radiolabeling of titanium 45 using mesoporous silica nanoparticles
Acta Pharmacologica Sinica, 2017Co-Authors: Feng Chen, Todd E. Barnhart, Shreya Goel, Hector F Valdovinos, Reinier Hernandez, Weibo CaiAbstract:Titanium-45 (45Ti) with a three-hour half-life (t1/2=3.08 h), low maximum positron energy and high positron emission branching ratio, is a suitable positron emission tomography (PET) isotope whose potential has not yet been fully explored. Complicated radiochemistry and rapid hydrolysis continue to be major challenges to the development of 45Ti compounds based on a traditional chelator-based Radiolabeling strategy. In this study we introduced an intrinsic (or chelator-free) Radiolabeling technique for the successful labeling of 45Ti using mesoporous silica nanoparticle (MSN). We synthesized uniform MSN with an average particle size of ∼150 nm in diameter. The intrinsic 45Ti-labeling was accomplished through strong interactions between 45Ti (hard Lewis acid) and hard oxygen donors (hard Lewis bases), the deprotonated silanol groups (-Si-O-) from the outer surface and inner meso-channels of MSN. In vivo tumor-targeted PET imaging of as-developed PEGylated [45Ti]MSN was further demonstrated in the 4T1 murine breast tumor-bearing mice. This MSN-based intrinsic Radiolabeling strategy could open up new possibilities and speed up the biomedical applications of 45Ti in the future.
Jason S. Lewis - One of the best experts on this subject based on the ideXlab platform.
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Click Chemistry and Radiochemistry: The First 10 Years
Bioconjugate Chemistry, 2016Co-Authors: Jan-philip Meyer, Pierre Adumeau, Jason S. Lewis, Brian M. ZeglisAbstract:The advent of click chemistry has had a profound influence on almost all branches of chemical science. This is particularly true of radiochemistry and the synthesis of agents for positron emission tomography (PET), single photon emission computed tomography (SPECT), and targeted radiotherapy. The selectivity, ease, rapidity, and modularity of click ligations make them nearly ideally suited for the construction of radiotracers, a process that often involves working with biomolecules in aqueous conditions with inexorably decaying radioisotopes. In the following pages, our goal is to provide a broad overview of the first 10 years of research at the intersection of click chemistry and radiochemistry. The discussion will focus on four areas that we believe underscore the critical advantages provided by click chemistry: (i) the use of prosthetic groups for Radiolabeling reactions, (ii) the creation of coordination scaffolds for radiometals, (iii) the site-specific Radiolabeling of proteins and peptides, and (iv...
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Enzyme-Mediated Methodology for the Site-Specific Radiolabeling of Antibodies Based on Catalyst-Free Click Chemistry
Bioconjugate Chemistry, 2013Co-Authors: Brian M. Zeglis, Brian J. Agnew, Aimei Chen, Hee Chol Kang, Robert Aggeler, Charles B. Davis, Jason S. LewisAbstract:An enzyme- and click chemistry-mediated methodology for the site-selective Radiolabeling of antibodies on the heavy chain glycans has been developed and validated. To this end, a model system based on the prostate specific membrane antigen-targeting antibody J591, the positron-emitting radiometal 89Zr, and the chelator desferrioxamine has been employed. The methodology consists of four steps: (1) the removal of sugars on the heavy chain region of the antibody to expose terminal N-acetylglucosamine residues; (2) the incorporation of azide-modified N-acetylgalactosamine monosaccharides into the glycans of the antibody; (3) the catalyst-free click conjugation of desferrioxamine-modified dibenzocyclooctynes to the azide-bearing sugars; and (4) the Radiolabeling of the chelator-modified antibody with 89Zr. The site-selective labeling methodology has proven facile, reproducible, and robust, producing 89Zr-labeled radioimmunoconjguates that display high stability and immunoreactivity in vitro (>95%) in addition ...
