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Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors. 小分子的氟-18标记:使用无载体添加[18F]氟化物衍生的18F标记的芳基氟化物作为标记前体。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-49527-7_3
F Wuest
{"title":"Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.","authors":"F Wuest","doi":"10.1007/978-3-540-49527-7_3","DOIUrl":"https://doi.org/10.1007/978-3-540-49527-7_3","url":null,"abstract":"<p><p>The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 62","pages":"51-78"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-49527-7_3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26446662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
Production of non-standard PET radionuclides and the application of radiopharmaceuticals labeled with these nuclides. 非标准PET放射性核素的生产和用这些核素标记的放射性药物的应用。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-49527-7_6
M J Welch, R Laforest, J S Lewis
{"title":"Production of non-standard PET radionuclides and the application of radiopharmaceuticals labeled with these nuclides.","authors":"M J Welch,&nbsp;R Laforest,&nbsp;J S Lewis","doi":"10.1007/978-3-540-49527-7_6","DOIUrl":"https://doi.org/10.1007/978-3-540-49527-7_6","url":null,"abstract":"<p><p>The field of positron emission tomography (PET) has expanded dramatically over recent years. In spite of this expansion the large majority of clinical studies are carried out utilizing one radiopharmaceutical-2-fluoro-2-deoxyglucose. Many research groups are developing novel radiopharmaceuticals. A major emphasis is on other agents labeled with 18F. Several other positron emitting radionuclides can be prepared in high yields in small biomedical cyclotrons. Some of these have half-lives that make delivery significantly easier than the delivery of 18F compounds. These radionuclides include: 64Cu (half life 12.7 h), 76Br (half life 16.2 h), 86Y (half life 14.74 h) and 124I (half life 4.2 days). The method of production of these and other 'non-standard' PET radionuclides will be discussed and the method of labeling radiopharmaceuticals with these radionuclides described. Several of these radiopharmaceuticals have been studied in animal models as well and a limited number translated to the human situation.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 62","pages":"159-81"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-49527-7_6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26446665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
RNAi applications in target validation. RNAi在靶标验证中的应用。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-31339-7_1
A Kourtidis, C Eifert, D S Conklin
{"title":"RNAi applications in target validation.","authors":"A Kourtidis,&nbsp;C Eifert,&nbsp;D S Conklin","doi":"10.1007/978-3-540-31339-7_1","DOIUrl":"https://doi.org/10.1007/978-3-540-31339-7_1","url":null,"abstract":"<p><p>The emergence of systems biology is certain to transform the identification and validation of therapeutic targets in modern drug discovery. A relatively recent systems biology approach is functional genomics, which identifies the molecular mechanisms responsible for a specific phenotype by interrogating the activity of all of an organism's genes. Initially undertaken in model organisms such as Caenorhabditis elegans, Saccharomyces cerevisiae, and Drosophila melanogaster, functional genomics has now moved into the realm of mammalian cells both in vitro and in vivo due to the development of RNA interference. RNA interference is a conserved biological process that has evolved to specifically and efficiently silence genes. Genome-wide screens using RNA interference have proven powerful in elucidating components of functionally related pathways and have therefore become integral for the development of new and improved therapeutic targets. This article provides an overview of many of the systems biology approaches taken, using RNA interference, in order to demonstrate how it may be used today for drug discovery and tomorrow as a targeted therapy.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 61","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-31339-7_1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26511249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Extrapolation of preclinical data into clinical reality translational science. 将临床前数据外推到临床现实转化科学。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-49529-1_1
T Singer
{"title":"Extrapolation of preclinical data into clinical reality translational science.","authors":"T Singer","doi":"10.1007/978-3-540-49529-1_1","DOIUrl":"https://doi.org/10.1007/978-3-540-49529-1_1","url":null,"abstract":"<p><p>Human and animal in vitro models are potentially powerful preclinical tools: prediction of pharmacological behaviour of drugs; selection of animal species most closely related to humans based on metabolic patterns; prediction of drug interactions and explanation of metabolic origins of interindividual variabilities in pharmacological activity. Extrapolation of preclinical data into clinical reality is a translational science and remains an ultimate challenge in drug development.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 59","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-49529-1_1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26375263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
The applications of biomarkers in early clinical drug development to improve decision-making processes. 生物标志物在早期临床药物开发中的应用,以改善决策过程。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-49529-1_3
J Kuhlmann
{"title":"The applications of biomarkers in early clinical drug development to improve decision-making processes.","authors":"J Kuhlmann","doi":"10.1007/978-3-540-49529-1_3","DOIUrl":"https://doi.org/10.1007/978-3-540-49529-1_3","url":null,"abstract":"<p><p>Selecting and evaluating biomarkers in drug discovery and early drug development can substantially shorten clinical development time or the time to reach a critical decision point in exploratory drug development. Critical decisions such as candidate selection, early proof of concept/principle, dose ranging, development risks, and patient stratification are based on the appropriate measurements of biomarkers that are biologically and/or clinically validated. The use of biomarkers helps to streamline clinical development by determining whether the drug is reaching and affecting the molecular target in humans, delivering findings that are comparable to preclinical data, and by providing a measurable endpoint that predicts desired or undesired clinical effects and will increase the success rate in the confirmatory stage of clinical development. Appropriateness of biomarkers depends on the stage of development, development strategy, and the nature of the medical indication. Even if a biomarker fails in the validation process there may be still a benefit of having used it. More knowledge about pathophysiology of the disease and the drug has been obtained. Different levels of validation exist at different development phases. Biomarkers are perhaps most useful in the early phase of clinical development when measurement of clinical endpoints may be too time-consuming or cumbersome to provide timely proof of concept or dose-ranging information. Examples of biomarkers are illustrated for the development of new drugs in variant cardiovascular, pulmonary, and CNS diseases.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 59","pages":"29-45"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-49529-1_3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26375265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 26
Microwaving in F-18 chemistry: quirks and tweaks. F-18化学中的微波:怪癖和调整。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-49527-7_9
S Stone-Elander, N Elander, J O Thorell, A Fredriksson
{"title":"Microwaving in F-18 chemistry: quirks and tweaks.","authors":"S Stone-Elander,&nbsp;N Elander,&nbsp;J O Thorell,&nbsp;A Fredriksson","doi":"10.1007/978-3-540-49527-7_9","DOIUrl":"https://doi.org/10.1007/978-3-540-49527-7_9","url":null,"abstract":"<p><p>Since the late 1980s, microwave dielectric heating has been used to speed up chemical transformations, also in radiolabeling tracers for positron emission tomography. In addition to shorter reaction times, higher yields, cleaner product mixtures and improved reproducibility have also been obtained for reactions involving polar components that require heating at elevated temperatures. The conditions used in microwave chemistry can differ considerably from those in conventional heating. Understanding the factors that influence the interaction of the electromagnetic field with the sample is critical for the successful implementation of microwave heating. These parameters are discussed here and exemplified with radiolabelings with fluorine-18.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 62","pages":"243-69"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-49527-7_9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26446556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 12
Fluorine-18 labeling methods: Features and possibilities of basic reactions. 氟-18标记方法:碱性反应的特点和可能性。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-49527-7_2
H H Coenen
{"title":"Fluorine-18 labeling methods: Features and possibilities of basic reactions.","authors":"H H Coenen","doi":"10.1007/978-3-540-49527-7_2","DOIUrl":"https://doi.org/10.1007/978-3-540-49527-7_2","url":null,"abstract":"<p><p>Many experimental and established tracers make fluorine- 18 the most widely used radionuclide in positron emission tomography with an increasing demand for new or simpler 18F-labeling procedures. After a brief summary of the advantages of the nuclide and its major production routes, the basic features of the principal radiofluorination methods are described. These comprise direct electrophilic and nucleophilic processes, or in case of more complex molecules, the labeling of synthons and prosthetic groups for indirect built-up syntheses. While addressing the progress of no-carrier-added 18F-labeling procedures, the following chapters on more specific topics in this book are introduced. Emphasis is given to radiofluorination of arenes--especially with iodonium leaving groups. Examples of radiopharmaceutical syntheses are mentioned in order to illustrate strategic concepts of labeling with fluorine-18.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 62","pages":"15-50"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-3-540-49527-7_2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26446661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 57
A plea for more theory in molecular biology. 对分子生物学更多理论的请求。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-31339-7_6
O Wolkenhauer, M Mesarović, P Wellstead
{"title":"A plea for more theory in molecular biology.","authors":"O Wolkenhauer,&nbsp;M Mesarović,&nbsp;P Wellstead","doi":"10.1007/978-3-540-31339-7_6","DOIUrl":"https://doi.org/10.1007/978-3-540-31339-7_6","url":null,"abstract":"<p><p>The integrationist principles of systems theory have proven hugely successful in the physical sciences and engineering. It is an underlying assumption made in the systems approach to biology that they can also be used to understand biological phenomena at the level of an entire organism or organ. Within this holistic vision, the vast majority of systems biology research projects investigate phenomena at the level of the cell, with the belief that unifying principles established at the most basic level can establish a framework within which we may understand phenomena at higher levels of organization. In this spirit, and to use a celestial analogy, if a disease--effecting an organ or entire body--is our universe of discourse, then the cell is the star we gaze at. In building an understanding of disease and the effect of drugs, systems biology makes an implicit assumption about direct causal entailment between cell function and physiology. A skeptic might argue that this is about the same as trying to predict the world economy from observations made at a local supermarket. However, assuming for the moment that the money and hope we are investing in molecular biology, genomics, and systems biology is justified, how should this amazing intellectual achievement be possible? In this chapter we argue that an essential tool to progress is a systems theory that allows biological objects and their operational characteristics to be captured in a succinct yet general form. Armed with this conceptual framework, we construct mathematical representations of standard cellular and intercellular functions which can be integrated to describe more general processes of cell complexes, and potentially entire organs.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 61","pages":"117-37"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26510662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
Does the serum peptidome reveal hemostatic dysregulation? 血清肽丘是否显示止血功能失调?
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-31339-7_2
M T Davis, S D Patterson
{"title":"Does the serum peptidome reveal hemostatic dysregulation?","authors":"M T Davis,&nbsp;S D Patterson","doi":"10.1007/978-3-540-31339-7_2","DOIUrl":"https://doi.org/10.1007/978-3-540-31339-7_2","url":null,"abstract":"<p><p>There is a significant need for markers that are diagnostic of disease, particularly cancer. For these biomarkers to be useful they would need to be able to detect disease early in its progression with high sensitivity and specificity. Many approaches are being undertaken to attempt to find such biomarkers using the tools of systems biology, i.e., parallel measurement techniques including proteomics (parallel protein measurements). Often the premise behind such an approach was to cast a wide net and then design an assay for specific elements that were found to be diagnostic. One such approach has utilized matrix-assisted laser desorption/ionization-mass spectrometry to interrogate the low-molecular-weight component of serum (the fluid component of blood following clotting), the serum peptidome. This approach has the appealing characteristic of speed of analysis but has a number of shortcomings mostly due to signal:noise and mass resolution in some instruments, making peak analysis difficult. Of course, experimental design and statistical analysis have to be conducted with the system limitations in mind. These points have been addressed by others, but few have focused on a potentially larger issue with serum peptidome analysis - are the signals being measured informing us about the disease state directly or indirectly through measurement of another physiological process such as hemostatic dysregulation? This article will present evidence that points to careful measures of the serum peptidome revealing differences in clotting time in disease states and not direct measures of tumor proteolytic activity on blood proteins.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 61","pages":"23-44"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26511250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 16
Systems biology: new paradigms for cell biology and drug design. 系统生物学:细胞生物学和药物设计的新范例。
Ernst Schering Research Foundation workshop Pub Date : 2007-01-01 DOI: 10.1007/978-3-540-31339-7_3
H V Westerhoff
{"title":"Systems biology: new paradigms for cell biology and drug design.","authors":"H V Westerhoff","doi":"10.1007/978-3-540-31339-7_3","DOIUrl":"https://doi.org/10.1007/978-3-540-31339-7_3","url":null,"abstract":"<p><p>In this chapter various facets of and approaches to systems biology will be discussed. This then leads to an illustration of how systems biology may be used in drug target design. We present five new paradigms for drug target research and show how these are based in systems biology.</p>","PeriodicalId":80277,"journal":{"name":"Ernst Schering Research Foundation workshop","volume":" 61","pages":"45-67"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26511251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
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