The Experts below are selected from a list of 2712 Experts worldwide ranked by ideXlab platform
Ralf Schirrmacher - One of the best experts on this subject based on the ideXlab platform.
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small prosthetic groups in 18f Radiochemistry useful auxiliaries for the design of 18f pet tracers
Seminars in Nuclear Medicine, 2017Co-Authors: Ralf Schirrmacher, Bjorn Wangler, Justin J Bailey, Vadim Bernardgauthier, Esther Schirrmacher, Carmen WanglerAbstract:Prosthetic group (PG) applications in 18F-Radiochemistry play a pivotal role among current 18F-labeling techniques for the development and availability of 18F-labeled imaging probes for PET (Wahl, 2002) (1). The introduction and popularization of PGs in the mid-80s by pioneers in 18F-Radiochemistry has profoundly changed the landscape of available tracers for PET and has led to a multitude of new imaging agents based on simple and efficiently synthesized PGs. Because of the chemical nature of anionic 18F- (apart from electrophilic low specific activity 18F-fluorine), Radiochemistry before the introduction of PGs was limited to simple nucleophilic substitutions of leaving group containing precursor molecules. These precursors were not always available, and some target compounds were either hard to synthesize or not obtainable at all. Even with the advent of recently introduced "late-stage fluorination" techniques for the 18F-fluorination of deactivated aromatic systems, PGs will continue to play a central role in 18F-Radiochemistry because of their robust and almost universal usability. The importance of PGs in Radiochemistry is shown by its current significance in tracer development and exemplified by an overview of selected methodologies for PG attachment to PET tracer molecules. Especially, click-chemistry approaches to PG conjugation, while furthering the historical evolution of PGs in PET tracer design, play a most influential role in modern PG utilization. All earlier and recent multifaceted approaches in PG development have significantly enriched the contingent of modern 18F-Radiochemistry procedures and will continue to do so.
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from unorthodox to established the current status of 18f trifluoroborate and 18f sifa based radiopharmaceuticals in pet nuclear imaging
Bioconjugate Chemistry, 2016Co-Authors: Vadim Bernardgauthier, Carmen Wangler, Bjorn Wangler, Justin J Bailey, Zhibo Liu, Klaus Jurkschat, David M Perrin, Ralf SchirrmacherAbstract:Unorthodox 18F-labeling strategies not employing the formation of a carbon-18F bond are seldom found in Radiochemistry. Historically, the formation of a boron- or silicon-18F bond has been introduced very early on into the repertoire of labeling chemistries, but is without translation into any clinical radiotracer besides inorganic B[18F]F4– for brain tumor diagnosis. For many decades these labeling methodologies were forgotten and have just recently been revived by a handful of researchers thinking outside the box. When breaking with established paradigms such as the inability to obtain labeled compounds of high specific activity via isotopic exchange or performing radiofluorination in aqueous media, the research community often reacts skeptically. In 2005 and 2006, two novel labeling methodologies were introduced into Radiochemistry for positron emission tomography (PET) tracer development: RBF3– labeling reported by Perrin et al. and the SiFA methodology by Schirrmacher, Jurkschat, and Waengler et al. ...
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synthesis of 3 chloro 6 4 di tert butyl 18f fluorosilyl benzyl oxy 1 2 4 5 tetrazine 18f sifa otz for rapid tetrazine based 18f radiolabeling
Chemical Communications, 2015Co-Authors: Jun Zhu, Carmen Wangler, Bjorn Wangler, Bruce R Lennox, Ralf SchirrmacherAbstract:An efficient method to prepare the 18F-labeled tetrazine-derivative [18F]-SiFA-OTz for bioorthogonal Radiochemistry was developed. [18F]-SiFA-OTz can be synthesized with a radiochemical yield of 78 ± 5% within 25 min and can quantitatively react with a model strained dienophile, trans-cyclooctenol.
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silicon 18f fluorine Radiochemistry basics applications and challenges
Applied Sciences, 2012Co-Authors: Carmen Wangler, Jun Zhu, Bjorn Wangler, Alexey Kostikov, Joshua Chin, Ralf SchirrmacherAbstract:Silicon-[18F]fluorine (Si-18F) Radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-18F and boron-18F based labeling strategies, reshaping the landscape of modern 18F-Radiochemistry. All these novel methodologies are driven by the demand for more convenient 18F-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as 18F (one of the most prominent examples) to be introduced into bioactive molecules. Si-18F Radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-18F bond formation, the application of Si-18F tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology.
Peter J H Scott - One of the best experts on this subject based on the ideXlab platform.
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development of customized 18f fluoride elution techniques for the enhancement of copper mediated late stage radiofluorination
Scientific Reports, 2017Co-Authors: Andrew V Mossine, Allen F Brooks, Naoko Ichiishi, Katarina J Makaravage, Melanie S Sanford, Peter J H ScottAbstract:In a relatively short period of time, transition metal-mediated radiofluorination reactions have changed the PET Radiochemistry landscape. These reactions have enabled the radiofluorination of a wide range of substrates, facilitating access to radiopharmaceuticals that were challenging to synthesize using traditional fluorine-18 Radiochemistry. However, the process of adapting these new reactions for automated radiopharmaceutical production has revealed limitations in fitting them into the confines of traditional Radiochemistry systems. In particular, the presence of bases (e.g. K2CO3) and/or phase transfer catalysts (PTC) (e.g. kryptofix 2.2.2) associated with fluorine-18 preparation has been found to be detrimental to reaction yields. We hypothesized that these limitations could be addressed through the development of alternate techniques for preparing [18F]fluoride. This approach also opens the possibility that an eluent can be individually tailored to meet the specific needs of a metal-catalyzed reaction of interest. In this communication, we demonstrate that various solutions of copper salts, bases, and ancillary ligands can be utilized to elute [18F]fluoride from ion exchange cartridges. The new procedures are effective for fluorine-18 Radiochemistry and, as proof of concept, have been used to optimize an otherwise base-sensitive copper-mediated radiofluorination reaction.
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fluorine 18 patents 2009 2015 part 2 new Radiochemistry
Pharmaceutical patent analyst, 2016Co-Authors: Andrew V Mossine, Allen F Brooks, Stephen Thompson, Alexandra R Sowa, Jason Miller, Peter J H ScottAbstract:Fluorine-18 (18F) is one of the most common positron-emitting radionuclides used in the synthesis of positron emission tomography radiotracers due to its ready availability, convenient half-life and outstanding imaging properties. In Part 1 of this review, we presented the first analysis of patents issued for novel radiotracers labeled with fluorine-18. In Part 2, we follow-up with a focus on patents issued for new Radiochemistry methodology using fluorine-18 issued between January 2009 and December 2015.
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ethanolic carbon 11 chemistry the introduction of green Radiochemistry
Applied Radiation and Isotopes, 2014Co-Authors: Xia Shao, Maria V Fawaz, Keunsam Jang, Peter J H ScottAbstract:The principles of green chemistry have been applied to a Radiochemistry setting. Eleven carbon-11 labeled radiopharmaceuticals have been prepared using ethanol as the only organic solvent throughout the entire manufacturing process. The removal of all other organic solvents from the process simplifies production and quality control (QC) testing, moving our PET Center towards the first example of a green Radiochemistry laboratory. All radiopharmaceutical doses prepared are suitable for clinical use.
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Radiosyntheses using Fluorine-18: the Art and Science of Late Stage Fluorination
Current Topics in Medicinal Chemistry, 2014Co-Authors: Erin L. Cole, Megan N. Stewart, Ryan Littich, Raphaël Hoareau, Peter J H ScottAbstract:Positron (β + ) emission tomography (PET) is a powerful, noninvasive tool for the in vivo, three-dimensional imaging of physiological structures and biochemical pathways. The continued growth of PET imaging relies on a corresponding increase in access to radiopharmaceuticals (biologically active molecules labeled with short-lived radionuclides such as fluorine-18). This unique need to incorporate the short-lived fluorine-18 atom (t 1/2 = 109.77 min) as late in the synthetic pathway as possible has made development of methodologies that enable rapid and efficient late stage fluorination an area of research within its own right. In this review we describe strategies for radiolabeling with fluorine-18, including classical fluorine-18 Radiochemistry and emerging techniques for late stage fluorination reactions, as well as labeling technologies such as microfluidics and solid-phase Radiochemistry. The utility of fluorine-18 labeled radiopharmaceuticals is showcased through recent applications of PET imaging in the healthcare, personalized medicine and drug discovery settings.
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Novel strategies for fluorine-18 Radiochemistry.
Angewandte Chemie International Edition, 2011Co-Authors: Ryan Littich, Peter J H ScottAbstract:Positron (b) emission tomography (PET) is a powerful, noninvasive tool for the in vivo, three-dimensional imaging of physiological structures and processes. PET imaging involves the incorporation of short-lived radionuclides, particularly carbon-11 and fluorine-18, into biologically active molecules. The resulting radiopharmaceuticals are introduced into human subjects, liberating positrons in the decay process that subsequently annihilate with electrons in adjacent matter. Detection of the g radiation generated during annihilation allows for well-defined images of ongoing bodily processes to be obtained. Understandably, wielding this technology— which requires the manipulation of strong radioemitters, short end-product efficacy timeframes, and rigorous quality control—is not a simple undertaking. In answer to this, and speaking to its clinical value, research pertaining to PET has observed exciting and rapid growth. The prospective applications for PET imaging are innumerable. Exploiting PET to its fullest potential has been limited, however, in large part, by the availability of pertinent radiopharmaceuticals. The identification of a suitable radionuclide for use in labeling is a concern intrinsic to the preparation of radiopharmaceutical agents. Carbon-11 and fluorine-18 are commonly used and each has its own merits. Radiolabeling with C has advantages that include minimal effects on substrate biological activity and ease of incorporation. C-radiolabeling also affords the ability to run multiple scans per day in series. However, C suffers from a rather short half-life (20 min) and susceptibility to environmental C contamination in processing. F finds utility in light of the fact that its incorporation into bioactive species sometimes affects their pharmacological profile. Fluorine-18 offers the benefit of a substantial half-life (about 110 min, allowing for distribution to satellite PET scan facilities), a clean decay process (97% b emission) and limited positron migration (about 1 mm, leading to highly resolved images). Indeed, F is ubiquitous in molecular imaging by positron emission tomography, as is exemplified by the success of [F]2-fluoro2-deoxy-d-glucose (FDG) in oncology research. [F]Fluoride is prepared by the proton bombardment of oxygen-18 enriched water through the nuclear reaction O(p,n)F. Aqueous solutions of F are rendered, from which the ion of interest can be isolated by ion-exchange chromatography. Gaseous [F]F2 is also available through the nuclear reaction Ne(d,a)F. The former facilitates nucleophilic fluorination reactions; the latter, electrophilic fluorination. Both reaction modes have important applications in PET imaging research. This article discusses recent strides in the field of F Radiochemistry, categorized by the reaction motif. Gouverneur and co-workers recently disclosed the preparation of [F]Selectfluor bis(triflate) 1 as a means to broaden the scope and utility of electrophilic fluorination for F Radiochemistry. Inspired by the mild, commercially available fluorinating agent Selectfluor, 1 was prepared through chloromethylation of diazabicyclo[2.2.2]octane, anion exchange, and subsequent fluorination using high-specific activity [F]F2 (Scheme 1). The resulting bis(triflate) was
Carmen Wangler - One of the best experts on this subject based on the ideXlab platform.
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small prosthetic groups in 18f Radiochemistry useful auxiliaries for the design of 18f pet tracers
Seminars in Nuclear Medicine, 2017Co-Authors: Ralf Schirrmacher, Bjorn Wangler, Justin J Bailey, Vadim Bernardgauthier, Esther Schirrmacher, Carmen WanglerAbstract:Prosthetic group (PG) applications in 18F-Radiochemistry play a pivotal role among current 18F-labeling techniques for the development and availability of 18F-labeled imaging probes for PET (Wahl, 2002) (1). The introduction and popularization of PGs in the mid-80s by pioneers in 18F-Radiochemistry has profoundly changed the landscape of available tracers for PET and has led to a multitude of new imaging agents based on simple and efficiently synthesized PGs. Because of the chemical nature of anionic 18F- (apart from electrophilic low specific activity 18F-fluorine), Radiochemistry before the introduction of PGs was limited to simple nucleophilic substitutions of leaving group containing precursor molecules. These precursors were not always available, and some target compounds were either hard to synthesize or not obtainable at all. Even with the advent of recently introduced "late-stage fluorination" techniques for the 18F-fluorination of deactivated aromatic systems, PGs will continue to play a central role in 18F-Radiochemistry because of their robust and almost universal usability. The importance of PGs in Radiochemistry is shown by its current significance in tracer development and exemplified by an overview of selected methodologies for PG attachment to PET tracer molecules. Especially, click-chemistry approaches to PG conjugation, while furthering the historical evolution of PGs in PET tracer design, play a most influential role in modern PG utilization. All earlier and recent multifaceted approaches in PG development have significantly enriched the contingent of modern 18F-Radiochemistry procedures and will continue to do so.
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from unorthodox to established the current status of 18f trifluoroborate and 18f sifa based radiopharmaceuticals in pet nuclear imaging
Bioconjugate Chemistry, 2016Co-Authors: Vadim Bernardgauthier, Carmen Wangler, Bjorn Wangler, Justin J Bailey, Zhibo Liu, Klaus Jurkschat, David M Perrin, Ralf SchirrmacherAbstract:Unorthodox 18F-labeling strategies not employing the formation of a carbon-18F bond are seldom found in Radiochemistry. Historically, the formation of a boron- or silicon-18F bond has been introduced very early on into the repertoire of labeling chemistries, but is without translation into any clinical radiotracer besides inorganic B[18F]F4– for brain tumor diagnosis. For many decades these labeling methodologies were forgotten and have just recently been revived by a handful of researchers thinking outside the box. When breaking with established paradigms such as the inability to obtain labeled compounds of high specific activity via isotopic exchange or performing radiofluorination in aqueous media, the research community often reacts skeptically. In 2005 and 2006, two novel labeling methodologies were introduced into Radiochemistry for positron emission tomography (PET) tracer development: RBF3– labeling reported by Perrin et al. and the SiFA methodology by Schirrmacher, Jurkschat, and Waengler et al. ...
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synthesis of 3 chloro 6 4 di tert butyl 18f fluorosilyl benzyl oxy 1 2 4 5 tetrazine 18f sifa otz for rapid tetrazine based 18f radiolabeling
Chemical Communications, 2015Co-Authors: Jun Zhu, Carmen Wangler, Bjorn Wangler, Bruce R Lennox, Ralf SchirrmacherAbstract:An efficient method to prepare the 18F-labeled tetrazine-derivative [18F]-SiFA-OTz for bioorthogonal Radiochemistry was developed. [18F]-SiFA-OTz can be synthesized with a radiochemical yield of 78 ± 5% within 25 min and can quantitatively react with a model strained dienophile, trans-cyclooctenol.
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silicon 18f fluorine Radiochemistry basics applications and challenges
Applied Sciences, 2012Co-Authors: Carmen Wangler, Jun Zhu, Bjorn Wangler, Alexey Kostikov, Joshua Chin, Ralf SchirrmacherAbstract:Silicon-[18F]fluorine (Si-18F) Radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-18F and boron-18F based labeling strategies, reshaping the landscape of modern 18F-Radiochemistry. All these novel methodologies are driven by the demand for more convenient 18F-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as 18F (one of the most prominent examples) to be introduced into bioactive molecules. Si-18F Radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-18F bond formation, the application of Si-18F tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology.
Bjorn Wangler - One of the best experts on this subject based on the ideXlab platform.
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small prosthetic groups in 18f Radiochemistry useful auxiliaries for the design of 18f pet tracers
Seminars in Nuclear Medicine, 2017Co-Authors: Ralf Schirrmacher, Bjorn Wangler, Justin J Bailey, Vadim Bernardgauthier, Esther Schirrmacher, Carmen WanglerAbstract:Prosthetic group (PG) applications in 18F-Radiochemistry play a pivotal role among current 18F-labeling techniques for the development and availability of 18F-labeled imaging probes for PET (Wahl, 2002) (1). The introduction and popularization of PGs in the mid-80s by pioneers in 18F-Radiochemistry has profoundly changed the landscape of available tracers for PET and has led to a multitude of new imaging agents based on simple and efficiently synthesized PGs. Because of the chemical nature of anionic 18F- (apart from electrophilic low specific activity 18F-fluorine), Radiochemistry before the introduction of PGs was limited to simple nucleophilic substitutions of leaving group containing precursor molecules. These precursors were not always available, and some target compounds were either hard to synthesize or not obtainable at all. Even with the advent of recently introduced "late-stage fluorination" techniques for the 18F-fluorination of deactivated aromatic systems, PGs will continue to play a central role in 18F-Radiochemistry because of their robust and almost universal usability. The importance of PGs in Radiochemistry is shown by its current significance in tracer development and exemplified by an overview of selected methodologies for PG attachment to PET tracer molecules. Especially, click-chemistry approaches to PG conjugation, while furthering the historical evolution of PGs in PET tracer design, play a most influential role in modern PG utilization. All earlier and recent multifaceted approaches in PG development have significantly enriched the contingent of modern 18F-Radiochemistry procedures and will continue to do so.
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from unorthodox to established the current status of 18f trifluoroborate and 18f sifa based radiopharmaceuticals in pet nuclear imaging
Bioconjugate Chemistry, 2016Co-Authors: Vadim Bernardgauthier, Carmen Wangler, Bjorn Wangler, Justin J Bailey, Zhibo Liu, Klaus Jurkschat, David M Perrin, Ralf SchirrmacherAbstract:Unorthodox 18F-labeling strategies not employing the formation of a carbon-18F bond are seldom found in Radiochemistry. Historically, the formation of a boron- or silicon-18F bond has been introduced very early on into the repertoire of labeling chemistries, but is without translation into any clinical radiotracer besides inorganic B[18F]F4– for brain tumor diagnosis. For many decades these labeling methodologies were forgotten and have just recently been revived by a handful of researchers thinking outside the box. When breaking with established paradigms such as the inability to obtain labeled compounds of high specific activity via isotopic exchange or performing radiofluorination in aqueous media, the research community often reacts skeptically. In 2005 and 2006, two novel labeling methodologies were introduced into Radiochemistry for positron emission tomography (PET) tracer development: RBF3– labeling reported by Perrin et al. and the SiFA methodology by Schirrmacher, Jurkschat, and Waengler et al. ...
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synthesis of 3 chloro 6 4 di tert butyl 18f fluorosilyl benzyl oxy 1 2 4 5 tetrazine 18f sifa otz for rapid tetrazine based 18f radiolabeling
Chemical Communications, 2015Co-Authors: Jun Zhu, Carmen Wangler, Bjorn Wangler, Bruce R Lennox, Ralf SchirrmacherAbstract:An efficient method to prepare the 18F-labeled tetrazine-derivative [18F]-SiFA-OTz for bioorthogonal Radiochemistry was developed. [18F]-SiFA-OTz can be synthesized with a radiochemical yield of 78 ± 5% within 25 min and can quantitatively react with a model strained dienophile, trans-cyclooctenol.
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silicon 18f fluorine Radiochemistry basics applications and challenges
Applied Sciences, 2012Co-Authors: Carmen Wangler, Jun Zhu, Bjorn Wangler, Alexey Kostikov, Joshua Chin, Ralf SchirrmacherAbstract:Silicon-[18F]fluorine (Si-18F) Radiochemistry has recently emerged alongside other unconventional approaches such as aluminum-18F and boron-18F based labeling strategies, reshaping the landscape of modern 18F-Radiochemistry. All these novel methodologies are driven by the demand for more convenient 18F-labeling procedures to further disseminate one of the most sophisticated imaging technologies, Positron Emission Tomography (PET). The PET methodology requires special radionuclides such as 18F (one of the most prominent examples) to be introduced into bioactive molecules. Si-18F Radiochemistry contributed greatly towards the development of new radiopharmaceuticals for PET imaging. Herein, we describe the radiochemical basics of Si-18F bond formation, the application of Si-18F tracers for PET imaging, and additionally, the inherent chemical intricacies of this methodology.
Neil Vasdev - One of the best experts on this subject based on the ideXlab platform.
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discovery of pet radiopharmaceuticals at the academia industry interface
Drug Discovery Today: Technologies, 2017Co-Authors: Vadim Bernardgauthier, Steven H Liang, Thomas Lee Collier, Neil VasdevAbstract:Project-specific collaborations between academia and pharmaceutical partners are a growing phenomenon within molecular imaging and in particular in the positron emission tomography (PET) radiopharmaceutical community. This cultural shift can be attributed in part to decreased public funding in academia in conjunction with the increased reliance on outsourcing of chemistry, Radiochemistry, pharmacology and molecular imaging studies by the pharmaceutical industry. This account highlights some of our personal experiences working with industrial partners to develop new PET Radiochemistry methodologies for drug discovery and neuro-PET research studies. These symbiotic academic-industrial partnerships have not only led to novel radiotracers for new targets but also to the application of new carbon-11 and fluorine-18 labeling methodologies and technologies to label previously unprecedented compounds for in vivo evaluations.
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brain penetration of the ros1 alk inhibitor lorlatinib confirmed by pet
Molecular Imaging, 2017Co-Authors: Lee T Collier, Kevin Maresca, Marc D Normandin, Paul G Richardson, Timothy J Mccarthy, Steven H Liang, Rikki Waterhouse, Neil VasdevAbstract:The Massachusetts General Hospital Radiochemistry Program, in collaboration with Pfizer, has developed unique 11C and 18F-labeling strategies to synthesize isotopologs of lorlatinib (PF-06463922) w...
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11co2 fixation a renaissance in pet Radiochemistry
Chemical Communications, 2013Co-Authors: Benjamin H Rotstein, Jason P Holland, Steven H Liang, Thomas Lee Collier, Jacob M Hooker, Alan A Wilson, Neil VasdevAbstract:Carbon-11 labelled carbon dioxide is the cyclotron-generated feedstock reagent for most positron emission tomography (PET) tracers using this radionuclide. Most carbon-11 labels, however, are installed using derivative reagents generated from [11C]CO2. In recent years, [11C]CO2 has seen a revival in applications for the direct incorporation of carbon-11 into functional groups such as ureas, carbamates, oxazolidinones, carboxylic acids, esters, and amides. This review summarizes classical [11C]CO2 fixation strategies using organometallic reagents and then focuses on newly developed methods that employ strong organic bases to reversibly capture [11C]CO2 into solution, thereby enabling highly functionalized labelled compounds to be prepared. Labelled compounds and radiopharmaceuticals that have been translated to the clinic are highlighted.