Therapeutic Alpha Emitters

Group Members


News

  • Toni Weber has sucessfully defended his Master thesis on December, 15th. Congratulations!
  • Laura Höffmann has sucessfully defended her Master thesis on October, 20th. Congratulations!
  • Paper describing the preparation of Lanthanum-133(6) as diagnostic radionuclide for Actinium-225 is out now. Congratulations Santiago!
  • We have received a grand from the Sander-Stiftung(7) starting from April 2022: Development of a Theranostic Concept for Radioconjugates on the Basis of the Alpha Emitter Actinium-225 for Oncological Issues.

Establishment of Alpha-emitting Radionuclides for Radiotherapeutics

AlphaTherapy(8)

Alpha-particle-emitting radionuclides are of high impact and interest for targeted radiotherapy for the treatment of cancer. Alpha particles are effective at killing cells due to their high linear energy transfer - LET (i.e. numerous, high-energy ionizations over a short path length in tissue), which results in a high relative biological effectiveness (RBE) which results in unrepairable DNA double-strand breaks that trigger cell death. Radium has two isotopes of interest for radiotherapy applications, Ra-223 (t1/2 = 11.5 d) and Ra-224 (t1/2 = 3.63 d). Both isotopes exhibit four α-decays and two β--decays in their decay chains with total emitted energies of 28 and 27 MeV, respectively. Additionally, Radium-223 is clinically approved by the EMA (European Medicines Agency) and FDA (Food & Drug Administration) as the free radium chloride(9) to treat bone metastases.

The challenge consists of the stable binding/complexation of radium (the heaviest group 2 element) and is inevitable to create radiotherapeutics. A release in vitro and in vivo should be avoided with this stable inclusion of the radium. Otherwise, bone uptake will occur. Two strategies were developed: the first consists of the complexation of Ra2+ with functionalized calix[4]arenes. Calixarenes, in general, as well as aza-crown ethers demonstrate good complexation of the group 2 elements. Barium is in use as a surrogate for radium to determine complexation stability and other properties. The second strategy involved the inclusion of the Ba2+/ Ra2+ into nanoparticle structures based on barium sulfate or with polyoxopalladate structures.

References:


New Labeling Strategies Using Staudinger Ligation and Click Chemistry

Click-Chemistry(20)

Bioorthogonal labeling reactions are important tools especially for the mild labeling of macromolecules (e.g. peptides, proteins, and antibodies) and reacting in aqueous environment. Due to the multitude of functional groups on these biomacromolecules, selective labeling reactions have to be developed to connect organic radionuclides ( e.g. fluorine-18) as well as radiometals (e.g. technetium-99m, rhenium-186/-188, and radium-223/-224) to these molecules without losing their biological/pharmacological impact. Labeling strategies based on the traceless Staudinger Ligation were developed to allow a site-selective labeling of azide- and alkyne-functionalized bio(macro)molecules.

References:


NMR Investigations of Chelating Ligands for Radiometals

Web-NMR(26)

Understanding the conformation of ligands and their complexes in terms of their (radio)chemical behavior is an important requirement to create stable complexes. For this purpose, two NMR devices (400 MHz and 600 MHz, Agilent Technologies) with ProbeOne and one in the control area (400 MHz, Varian) are available. Additionally, NMR techniques are in use to determine complexation constants for e. g. barium complexes (as a surrogate for radium). This work supports the development of a stable radium complex for targeted radiotherapy.

References:


Former Group Members

  • Falco Reissig (MSc, HTW Dresden, 2017; PhD(32), TU Dresden, 2021; PostDoc, 2023)
  • Jan Faltejsek (exchange student, Charles University in Prague, 2023)
  • Toni Weber (MSc, TU Dresden, 2022)
  • Laura Höffmann (MSc, TU Dresden, 2022)
  • Marlene Schlesinger (MSc, Uni Leipzig, 2022)
  • Ingmar Habel (BSc, HTW Dresden, 2022, supervision by Dr. Falco Reissig)
  • Tobias Krönke (BSc, TU Dresden, 2021)
  • David Bauer(33) (PhD(34), TU Dresden, 2020)
  • Patrick Wieder (chemical laboratory assistant till 2020)
  • Waldemar Herzog (chemical laboratory assistant till 2020)
  • Alina Pisarevskaja (MSc, TU Dresden, 2019, supervision by Dr. A. Heller - Faculty of Biology)
  • Erik Eiselt (MSc, HTW Dresden, 2019)
  • Markus Blumberg (MSc, TU Dresden, 2019)
  • Stepan Geri (MSc, TU Dresden, 2019, with Dr. M. Kubeil and Dr. H. Stephan)
  • Katie Manas (internship, RISE exchange program DAAD(35), Queen's University, Kingston, Canada, summer 2019)
  • Vincent Hocke (MSc, HTW Dresden, 2018)
  • Dr. Matthew Gott (PostDoc, 2015-2017)
  • Janine Steinberg (diploma, TU Dresden, 2017)
  • Sergej Stipurin (MSc, TU Dresden, 2017)
  • Jaques Pliquett (MSc, Université de Bordeaux, 2015, with Prof. P. Fernandez)
  • Doreen Pietzsch (PhD(36), TU Dresden, 2015, with Prof. Dr. J. Pietzsch)
  • Jens Wiemer (MSc, HTW Dresden, 2014)
  • Marc Pretze(37) (PhD(38), TU Dresden, 2014)
  • Madelaine Müller (BSc, TU Dresden, 2013)
  • Jean-Noel Grad (MSc, ENSICAEN - Frankreich, 2013)
  • Maria Weißpflog (bachelor, HTW Dresden, 2012, with Dr. H. Stephan)
  • Elisa Kinski (diploma, HS Zittau-Görlitz, 2012, price for the best diploma thesis)
  • Kristin Ebert (diploma, HS Zittau-Görlitz, 2012)
  • Marc Pretze (diploma, TU Dresden, 2009)
  • Philipp Große-Gehling (diploma, HTW Dresden, 2008)
  • Stefan Büttner (diploma, Uni Greifswald, 2007, with Prof. P. Langer)
  • Tianan Trabhardt (diploma, Uni Rostock, 2007, with Prof. P. Langer)
  • Mathias Lubbe (diploma, 2006, Uni Rostock, with Prof. P. Langer)
  • Anke Flemming (diploma, Uni Rostock, 2005, with Prof. R. Miethchen)

URL of this article
https://www.hzdr.de/db/Cms?pOid=54411


Contact

Dr. habil. Constantin Mamat

Research Associate
Medical Radiochemistry
c.mamatAthzdr.de
Phone: +49 351 260 2805
+49 351 260 2313

Dr. Sven Stadlbauer

Head of Department Medicinal Radiochemistry
s.stadlbauerAthzdr.de
Phone: +49 351 260 3249


More information

Funding: https://www.wilhelm-sander-stiftung.de/
Latest Publication: https://doi.org/10.1021/acs.inorgchem.3c01983
Latest Publication: https://doi.org/10.1039/D2QI01637K


Links of the content

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(2) https://orcid.org/0000-0003-1906-3186
(3) https://www.researchgate.net/profile/Constantin_Mamat
(4) https://www.hzdr.de/db/!ContMan.Visi.Card?pNid=no&pUser=123978
(5) https://www.hzdr.de/db/!ContMan.Visi.Card?pNid=no&pUser=139428
(6) https://doi.org/10.3390/ph15101167
(7) https://www.wilhelm-sander-stiftung.de/
(8) https://www.hzdr.de/db/PicOri?pOid=55009
(9) http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002653/WC500156174.pdf
(10) https://www.mdpi.com/2072-6694/13/8/1974
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(12) https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra07293d#!divAbstract
(13) https://pubs.rsc.org/en/Content/ArticleLanding/2019/CC/C9CC02587A#!divAbstract
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(19) https://doi.org/10.1515/chem-2016-0011
(20) https://www.hzdr.de/db/PicOri?pOid=55010
(21) https://doi.org/10.3390/molecules26216629
(22) https://doi.org/10.1002/jlcr.3562
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(30) https://doi.org/10.1002/kin.21137
(31) https://www.beilstein-journals.org/bjoc/articles/12/242
(32) https://tud.qucosa.de/id/qucosa:76430
(33) https://www.sloankettering.edu/research-areas/labs/members/david-bauer
(34) https://katalog.slub-dresden.de/id/0-1701062690/#detail
(35) https://www.daad.de/rise/en/
(36) https://katalogbeta.slub-dresden.de/id/0013714894/#detail
(37) https://www.researchgate.net/profile/Marc-Pretze
(38) http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-148062