Projects and Aims
Establishment of Alpha-emitting Radionuclides for Radiotherapeutics
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 a-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 to treat bone metastases.
The challenge consists in the stable binding/complexation of radium (a group 2 element) 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 calixarenes. 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 polyoxopalladate structures.
- M. Gott, J. Steinbach, C. Mamat, Open Chem. 2016, 14, 118–129- J. Steinberg, M. Gott, H.-J. Pietzsch, J. Steinbach, C. Mamat, J. Labelled Compd. Radiopharm. 2016, 60, S488
- M. Gott, P. Yang, U. Kortz, H.-J. Pietzsch, J. Steinbach, C. Mamat, J. Labelled Compd. Radiopharm. 2016, 60, S559
New Labeling Strategies Using Staudinger Ligation and Click Chemistry
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.
- M. Pretze, D. Pietzsch, C. Mamat, Molecules 2013, 18, 8618
- C. Mamat, M. Franke, T. Peppel, M. Köckerling, J. Steinbach, Tetrahedron 2011, 67, 4521
- C. Mamat, T. Ramenda, F. R. Wuest, Mini-Rev. Org. Chem. 2009, 6, 21
NMR Investigations of Chelating Ligands for Radiometals
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 ligand complexes (as a surrogate for radium). This work supports the development of a stable radium complex for targeted radiotherapy.
- C. Mamat, M. Pretze, M. Gott, M. Köckerling, Beilstein J. Org. Chem. 2016, 12, 2478
- M. Köckerling, C. Mamat, Int. J. Chem. Kinetics 2017, accepted
Dr. Constantin Mamat (head of the group)
Dr. Matthew Gott (PostDoc)
David Bauer (Ph.D. student)
Falco Reissig (master student)
Patrick Wieder (chemical laboratory assistant)
former group members
Janine Steinberg (diploma student) 2017
Sergej Stipurin (master student) 2017