Special Issue "Radiopharmaceutical Chemistry between Imaging and Radioendotherapy"
A special issue of Pharmaceuticals (ISSN 1424-8247).
Deadline for manuscript submissions: 15 December 2013
Prof. Dr. Klaus Kopka
Division of Radiopharmaceutical Chemistry, Research Program Imaging and Radiooncology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
Interests: radiopharmaceutical sciences; labeling chemistry; medicinal chemistry; PET tracers; radiopharmaceuticals for diagnostics and radioendotherapy; small molecules; peptides; antibodies and derivatives thereof
The journal “Pharmaceuticals” is planning to publish a special issue covering the topic “Radiopharmaceutical Chemistry between Imaging and Radioendotherapy” and I am cordially inviting you to contribute an article to this volume.
Positron emission tomography (PET), single photon emission computed tomography (SPECT), and the combined imaging modalities realised in the en-vogue hybrid technologies PET/CT and PET/MR represent the state-of-the-art diagnostic imaging technologies in nuclear medicine which are used for the highly sensitive non-invasive imaging of biological processes at the subcellular and molecular level in a respective patient for the visualisation of rather early disease states or for early inspection of treatment response after chemotherapy, radiation- or radioendotherapy.
Radiolabelled molecules, bearing a “radioactive lantern”, function as so called Radiopharmaceuticals which have to be compliant with the pharmaceuticals act, and can be termed as “food” of nuclear medicine. In general, the specialised field Radiopharmaceutical Chemistry focusses on the development, synthesis and radiolabelling of aforementioned “food”, such as small molecules, biotechnology-derived antibodies or (cyclised) (oligo)peptides which are used to address clinically relevant biological “downstream” targets such as receptors, enzymes, transport systems and others. Addressing “upstream” targets such as DNA- and RNA-fragments using corresponding radioactive substrates represents a further feasible strategy.
Originally, Radiopharmaceutical Chemistry descends from radiochemistry and radiopharmacy as well as nuclear chemistry and uses methods finally aiming at the production of radioactive substances for human application which are essential for non-invasive in vivo imaging by means of the aforementioned scintigraphic methods PET or SPECT.
The cornerstone for applicable radiochemistry in nuclear medicine was set by the Hungarian chemist George Charles de Hevesy who received the Nobel Prize in 1943 for his work on the radioindicator principle. This principle is based on the idea that the absolute amount of the administered substance is below the dose needed to induce a pharmacodynamic effect. Nowadays, a radioactive substance that can be traced in vivo as it moves through the living organism is termed radiotracer or radiopharmaceutical. As mentioned above, the biodistribution of radiopharmaceuticals is measured non-invasively reflecting functional or molecular disorders without pharmacologically affecting the organism.
In the era of personalised medicine the diagnostic potential of radiopharmaceuticals is directly linked to a subsequent individual therapeutic approach called radioendotherapy. Depending on the “radioactive lantern” (gamma or particle emitter) used for radiolabelling of the respective tracer molecule, the field Radiopharmaceutical Chemistry can contribute to the set-up of an in vivo “theranostic” approach especially in tumour patients by offering tailor-made (radio)chemical entities labelled either with a diagnostic or a therapeutic radionuclide.
To succeed in the design of targeted high-affinity radiopharmaceuticals that can measure the alteration of receptors serving at the same time as biological targets for individualised radioendotherapy several aspects need to be considered: (i) reasonable pharmacological behaviour (especially pharmacokinetics adjusted to the physical half-life of the used radionuclide), (ii) ability to penetrate and cross biological membranes, (iii) usage of chemical as well as biological amplification strategies (e.g. pretargeting, biological trapping of converted ligands, change of the physicochemical behaviour of the radiopharmaceutical after target interaction, combination with biotransporters and heterodimer approaches), (iv) availability of radiopharmaceuticals with high specific activities and in vivo stability.
I would like you to share your contributions to the advances and opportunities in this highly recognised field Radiopharmaceutical Chemistry located between personalised non-invasive imaging and radioendotherapy for this special issue. Areas of interest include:
- Feasible radionuclides and their production for direct or indirect radiolabelling of diagnostic and therapeutic radiopharmaceuticals including usage of prosthetic groups/radiosynthons,
- Small (non-peptide) molecule-derived radiopharmaceuticals (PET and SPECT),
- Biotechnology-derived radiopharmaceuticals (e.g. antibodies and derivatives thereof, fragments, affibodies, diabodies, (oligo)peptides) (PET and SPECT),
- in vivo targeting strategies by chemical modification considering maintained target specificity and improved pharmacokinetics (e.g. SAR studies on lead structures, multimerisation yes or no, influence of linkers/spacers and chelators, molecular transporters, heterodimerisation),
- Comparison of preclinical and clinical in vivo evaluations of respective radiotracers/radiopharmaceuticals (e.g. small-animal PET vs. human PET),
- Examples of radiopharmaceuticals in oncology: in vivo “theranostic” approaches.
Prof. Dr. Klaus Kopka
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Article
Title: Asymmetric Synthesis of Spirocyclic 2-Benzopyrans for the Positron Emission Tomography of σ1 Receptors in the Brain
Authors: Katharina Holl 1, Dirk Schepmann 1, Steffen Fischer 2, Achim Hiller 2, Winnie Deuther-Conrad 2, Peter Brust 2, Bernhard Wünsch 1,*
Affiliations: 1 Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Corrensstraße 48, D-48149 Münster, Germany; Tel.: +49-251-8333311; Fax: +49-251-8332144
2 Helmholtz-Zentrum Dresden-Rossendorf, Institut für Radiopharmazeutische Krebsforschung Forschungsstelle Leipzig, Abteilung Neuroradiopharmaka, Permoserstraße 15, D-04318 Leipzig, Germany
Abstract: Sharpless asymmetric dihydroxylation of styrene derivative 6 afforded the chiral triol 7, which were cyclized with tosyl chloride in the presence of Bu2SnO to form 2-benzopyrans 8 with an additional hydroxy moiety in 4-position. Williamson ether synthesis and exchange of the Boc protective group against a benzyl moiety led to potent σ1 ligands with high σ1/σ2-selectivity. (R)- and (S)-configured 2-benzopyrans with a 4-ethoxy, 4-hydroxyethoxy or 4-fluoroethoxy substituent show almost the same σ1 affinity. However, the σ1 receptor is able to differentiate between enantiomeric 2-benzopytans with a small substituent in 4-position (OH, OCH3). The methyl ether 8a represents the most potent σ1 ligand with a Ki value of 1.2 nM and an eudismic ratio of 7. Tosylate (S)-12 was used as precursor for the radiosynthesis of [18F]-(S)-13, which was available by nucleophilic substitution with K[18F]F K222-comüplex in high radiochemical yields and radiochemical purity. In in vivo studies [18F]-(S)-13 labeled selectively σ1 receptors. Radiolmetabolites of [18F]-(S)-13 were not detected.
Last update: 12 August 2013