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  1. Book ; Online: In Vivo Imaging in Pharmacological Research

    Windhorst, Albert D. / Kaltashov, Igor A. / Beckmann, Nicolau

    2017  

    Abstract: The discovery and development of a biological active molecule with therapeutic properties is an ever increasing complex task, highly unpredictable at the early stages and marked, in the end, by high rates of failure. As a consequence, the overall process ...

    Abstract The discovery and development of a biological active molecule with therapeutic properties is an ever increasing complex task, highly unpredictable at the early stages and marked, in the end, by high rates of failure. As a consequence, the overall process leading to the production of a successful drug is very costly. The improvement of the net outcome in drug discovery and development would require, amongst other important factors, a good understanding of the molecular events that characterize the disease or pathology in order to better identify likely targets of interest, to optimize the interaction of an active agent (small molecule or macromolecule of natural or synthetic origin) with those targets, and to facilitate the study of the pharmacokinetics, pharmacodynamics and toxicity of an active agent in suitable models and in human subjects. The objective of this Research Topic is to highlight new developments and applications of imaging techniques with the objective of performing pharmacological studies in vivo, in animal models and in humans. In the domain of drug discovery, the pharmacological and biomedical questions constitute the center of attention. In this sense, it is fundamental to keep in mind the strengths and limitations of each analytical or imaging technique. At the end, the judicious application of the technique with the aim of supporting the search for answers to manifold questions arising during a long and painstaking path provides a continuous role for imaging within the complex area of drug discovery and development
    Keywords Therapeutics. Pharmacology ; Science (General)
    Size 1 electronic resource (222 p.)
    Publisher Frontiers Media SA
    Document type Book ; Online
    Note English ; Open Access
    HBZ-ID HT020095941
    ISBN 9782889452378 ; 2889452379
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  2. Article ; Online: Synthesis of 18F-labeled Aryl Trifluoromethyl Sulfones, -Sulfoxides, and -Sulfides for Positron Emission Tomography.

    Veth, Lukas / Windhorst, Albert D / Vugts, Danielle J

    Angewandte Chemie (International ed. in English)

    2024  , Page(s) e202404278

    Abstract: Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is ... ...

    Abstract Positron emission tomography (PET) is becoming increasingly important in nuclear medicine and drug discovery. To date, the development of many potential PET tracers is hampered by the lack of suitable synthetic pathways for their preparation. This is particularly true for the highly desired radiolabeling of compounds bearing [18F]CF3-groups. For instance, S(O)nCF3-groups (n = 0, 1, 2) serve as structural motif in a range of biologically active compounds, but their radiosynthesis remains largely unprecedented (for n = 1, 2). Herein, we describe general methods for the radiosynthesis of 18F-labeled aryl trifluoromethyl sulfones, -sulfoxides, and -sulfides. All three methods are operationally straightforward, start from widely available precursors, i.e., sulfonyl fluorides and thiophenols, and make use of the recently established [18F]Ruppert-Prakash reagent. Further, the syntheses display good functional group tolerance as demonstrated by the 18F-labeling of more than 40 compounds. The applicability of the new method is demonstrated by the radiolabeling of three bioactive molecules, optionally to be used as PET tracers. In a broader context, this work presents a substantial expansion of the chemical space of radiofluorinated structural motifs to be used for the development of new PET tracers.
    Language English
    Publishing date 2024-04-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.202404278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: State of the art procedures towards reactive [

    Haveman, Lizeth Y F / Vugts, Danielle J / Windhorst, Albert D

    EJNMMI radiopharmacy and chemistry

    2023  Volume 8, Issue 1, Page(s) 28

    Abstract: Background: Positron emission tomography (PET) is a powerful, non-invasive preclinical and clinical nuclear imaging technique used in disease diagnosis and therapy assessment. Fluorine-18 is the predominant radionuclide used for PET tracer synthesis. An ...

    Abstract Background: Positron emission tomography (PET) is a powerful, non-invasive preclinical and clinical nuclear imaging technique used in disease diagnosis and therapy assessment. Fluorine-18 is the predominant radionuclide used for PET tracer synthesis. An impressive variety of new 'late-stage' radiolabeling methodologies for the preparation of
    Main body: Despite these developments, one outstanding challenge into the early key steps of the process remains: the preparation of reactive [
    Conclusion: Improved, modified or even completely new fluorine-18 work-up procedures have been developed in the last decade with widespread use in base-sensitive nucleophilic
    Language English
    Publishing date 2023-10-12
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2365-421X
    ISSN (online) 2365-421X
    DOI 10.1186/s41181-023-00203-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Enantioselective Synthesis of Carbon-11-Labeled Amino Acids and Peptides.

    Pekošak, Aleksandra / Windhorst, Albert D / Poot, Alex J

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2729, Page(s) 15–27

    Abstract: Radiolabeled amino acids (AAs), their derivatives, and peptides are essential radiotracers in nuclear imaging. Despite its potential, the preparation of enantiopure radiopharmaceuticals poses several challenges, demanding a great need for rapid and ... ...

    Abstract Radiolabeled amino acids (AAs), their derivatives, and peptides are essential radiotracers in nuclear imaging. Despite its potential, the preparation of enantiopure radiopharmaceuticals poses several challenges, demanding a great need for rapid and stereocontrolled reactions. This chapter describes a highly stereoselective carbon-11 alkylation of Schiff bases, to obtain radiolabeled AAs and small peptides. The method uses chiral quaternary ammonium salt phase-transfer catalyst with two alkylating agents, namely, [
    MeSH term(s) Amino Acids/chemistry ; Stereoisomerism ; Carbon Radioisotopes ; Peptides/chemistry
    Chemical Substances Amino Acids ; Carbon-11 ; Carbon Radioisotopes ; Peptides
    Language English
    Publishing date 2023-11-25
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3499-8_2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Synchronizing chemistry, quantum mechanics and radioactivity in a revolutionary renewed atom model. Part 1: the elements where Z is 1–10 (H, He, Li, Be, B, C, N, O, F, Ne)

    Visser, Gerard W. M. / Windhorst, Albert D.

    RSC advances. 2021 Aug. 19, v. 11, no. 45

    2021  

    Abstract: The alliance between the reigning quantum mechanical atom model and chemistry still is a difficult one when it comes to an adequate explanation for e.g. the covalent bond, inversion, chirality, or hydrogen bonds. Overruling Rutherford's extrapolation ... ...

    Abstract The alliance between the reigning quantum mechanical atom model and chemistry still is a difficult one when it comes to an adequate explanation for e.g. the covalent bond, inversion, chirality, or hydrogen bonds. Overruling Rutherford's extrapolation from gold to hydrogen, an atom model is described that provides improved answers to these phenomena while the hybridization principle and the covalent bond are re-defined by giving neutrons a much more prominent role than they have in the reigning quantum mechanical model. It is postulated that a neutron is not just there to assist the strong force in surpassing the repulsive coulombic forces between the protons in the nucleus, but the neutron is the modus operandi of molecular geometry, and as such plays a part in chemical reactivity, bond length and bond strength.
    Keywords geometry ; gold ; hydrogen ; mechanical models ; neutrons ; optical isomerism ; quantum mechanics ; radioactivity
    Language English
    Dates of publication 2021-0819
    Size p. 27978-27991.
    Publishing place The Royal Society of Chemistry
    Document type Article
    ISSN 2046-2069
    DOI 10.1039/d1ra03529k
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Synchronizing chemistry, quantum mechanics and radioactivity in a revolutionary renewed atom model. Part 1: the elements where

    Visser, Gerard W M / Windhorst, Albert D

    RSC advances

    2021  Volume 11, Issue 45, Page(s) 27978–27991

    Abstract: The alliance between the reigning quantum mechanical atom model and chemistry still is a difficult one when it comes to an adequate explanation ... ...

    Abstract The alliance between the reigning quantum mechanical atom model and chemistry still is a difficult one when it comes to an adequate explanation for
    Language English
    Publishing date 2021-08-19
    Publishing country England
    Document type Journal Article
    ISSN 2046-2069
    ISSN (online) 2046-2069
    DOI 10.1039/d1ra03529k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: [11C]CO2 BOP fixation with amines to access 11C-labeled ureas for PET imaging.

    Bonnemaire, Coralie M / Windhorst, Albert D / Orru, Romano / Ruijter, Eelco / Vugts, Danielle J

    Journal of labelled compounds & radiopharmaceuticals

    2023  Volume 67, Issue 6, Page(s) 201–210

    Abstract: Carbon-11 ( ...

    Abstract Carbon-11 (
    MeSH term(s) Carbon Radioisotopes/chemistry ; Positron-Emission Tomography/methods ; Urea/chemistry ; Amines/chemistry ; Carbon Dioxide/chemistry ; Organophosphorus Compounds/chemistry ; Organophosphorus Compounds/chemical synthesis ; Isotope Labeling ; Radiopharmaceuticals/chemical synthesis ; Radiopharmaceuticals/chemistry
    Language English
    Publishing date 2023-12-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 196095-7
    ISSN 1099-1344 ; 0362-4803 ; 0022-2135
    ISSN (online) 1099-1344
    ISSN 0362-4803 ; 0022-2135
    DOI 10.1002/jlcr.4075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: The Development of Positron Emission Tomography Tracers for In Vivo Targeting the Kinase Domain of the Epidermal Growth Factor Receptor.

    Högnäsbacka, Antonia / Poot, Alex J / Vugts, Danielle J / van Dongen, Guus A M S / Windhorst, Albert D

    Pharmaceuticals (Basel, Switzerland)

    2022  Volume 15, Issue 4

    Abstract: Multiple small molecule PET tracers have been developed for the imaging of the epidermal growth factor receptor (EGFR). These tracers target the tyrosine kinase (TK) domain of the receptor and have been used for both quantifying EGFR expression and to ... ...

    Abstract Multiple small molecule PET tracers have been developed for the imaging of the epidermal growth factor receptor (EGFR). These tracers target the tyrosine kinase (TK) domain of the receptor and have been used for both quantifying EGFR expression and to differentiate between EGFR mutational statuses. However, the approaches for in vivo evaluation of these tracers are diverse and have resulted in data that are hard to compare. In this review, we analyze the historical development of the in vivo evaluation approaches, starting from the first EGFR TK PET tracer [
    Language English
    Publishing date 2022-04-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph15040450
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers.

    Palard-Novello, Xavier / Visser, Denise / Tolboom, Nelleke / Smith, Charlotte L C / Zwezerijnen, Gerben / van de Giessen, Elsmarieke / den Hollander, Marijke E / Barkhof, Frederik / Windhorst, Albert D / van Berckel, Bart Nm / Boellaard, Ronald / Yaqub, Maqsood

    EJNMMI physics

    2024  Volume 11, Issue 1, Page(s) 25

    Abstract: Background: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds ... ...

    Abstract Background: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings.
    Methods: Eight [
    Results: For [
    Conclusions: For [
    Language English
    Publishing date 2024-03-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2768912-8
    ISSN 2197-7364
    ISSN 2197-7364
    DOI 10.1186/s40658-024-00628-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Structural basis of ligand recognition and design of antihistamines targeting histamine H

    Xia, Ruixue / Shi, Shuang / Xu, Zhenmei / Vischer, Henry F / Windhorst, Albert D / Qian, Yu / Duan, Yaning / Liang, Jiale / Chen, Kai / Zhang, Anqi / Guo, Changyou / Leurs, Rob / He, Yuanzheng

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2493

    Abstract: The histamine ... ...

    Abstract The histamine H
    MeSH term(s) Histamine/metabolism ; Drug Inverse Agonism ; Receptors, Histamine H4 ; Receptors, G-Protein-Coupled/metabolism ; Ligands ; Receptors, Histamine/metabolism ; Histamine Antagonists/pharmacology ; Imidazoles ; Thiourea/analogs & derivatives
    Chemical Substances clobenpropit (RKU631JF4H) ; Histamine (820484N8I3) ; Receptors, Histamine H4 ; Receptors, G-Protein-Coupled ; Ligands ; Receptors, Histamine ; Histamine Antagonists ; Imidazoles ; Thiourea (GYV9AM2QAG)
    Language English
    Publishing date 2024-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46840-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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