Tumor specific PET radiotracer
Projects and Aims
Novel Labeling Strategies
... via Staudinger Ligation and Click-Chemistry
Bioorthogonal reactions are an important tool to label biomacromolecules. Due to the presence of numerous functional groups, methods that enable the selective introduction of the radionuclides fluorine-18 and carbon-11 into these molecules are required. To this end, we developed strategies based on the traceless Staudinger ligation allowing the selective radiolabelling of azido-functionalized molecules.
- C. Mamat, M. Franke, T. Peppel, M. Köckerling, J. Steinbach Tetrahedron 2011, 67, 4521-4529
- M. Pretze, A. Flemming, M. Köckerling, C. Mamat Z. Naturforsch. B. 2010, 65b, 1128–1136- M. Pretze, F. Wuest, T. Peppel, M. Köckerling, C. Mamat Tetrahedron Lett. 2010, 51, 6410–6414
... for the selective Introduction of Fluorine-18 into peptides
A solid phase-based approach for the site-selective introduction of fluorine-18 into peptides containing multiple amino groups is developed.
- M. Kuchar, M. Pretze, C. Mamat, T. Knieß, J. Steinbach, R. Löser J. Labelled Compd. Radiopharm. 2011, 54, S449
... by sulfonamides as prosthetic groups
The radiosynthesis of 3-[18F]fluoropropanesulfonyl chloride was established and their reaction with aliphatic and aromatic amines optimised.
- R. Löser, A. Hiller, S. Fischer, U. Funke, A. Maisonial, P. Brust, J. Steinbach, J. Labelled Compd. Radiopharm. 2011, 54, S477
Development and Radiofluorination of Eph Receptor Inhibitors
The communication of Eph receptors and their ephrin ligands is of crucial importance for several pathophysoliogical processes such as tumourigenesis. An upregulation of both the ephrin ligands as well as the Eph receptors has been found for breast, liver and prostate cancer as well as for melanomas. Peptides mimicking ephrin ligands are used to develop fluorine-18 based tracers enabling the imaging of tumour cells overexpressing the EphB4 receptor. In a different approach, benzodioxolylpyrimidines targeting the kinase domain of the EphB4 receptor could be identified and are labelled with fluorine-18 to evaluate their potential as imaging agents.
- C. Neuber, B. Mosch, C. Mamat, J. Pietzsch Eur. J. Cancer Suppl. 2010, 8, 120–121
Development of PET tracers to characterise the metastatic potential of tumours
The lethal potential of cancer is mainly due to the invasive growth of tumours. Processes of tumour invasion and metastasis are closely linked to structural changes in the extracellular matrix. One key player in matrix restructuring is the enzyme lysyl oxidase. Therefore, one project is devoted to the development of radioactive probes that allow to visualise the activity of this enzyme in vivo. This is also including the establishment of biochemical methods to identify suitable compounds.
Proteases are of paramount importance for tumour metastasis. Beside matrix metalloproteases thiol-dependent cathepsins are involved. Thus, a further project is directed towards the development of fluorine-18 and carbon-11 labelled inhibitors of these proteases to assess the invasive potential of tumours in vivo.
- R. Löser, M. Frizler, K. Schilling, M. Gütschow Angew. Chem. 2008, 120, 4403–4406
- R. Löser, M. Frizler, R. Bergmann, L. Dombrowski, T. Knieß, M. Gütschow, J. Steinbach, J. J. Labelled Compd. Radiopharm. 2011, 54, S190
Interested in Bachelor, Master or Diploma Theses?
Dr. Reik Löser (head)
Kristin Ebert (Diploma-Student)
Jan Kiebist (Bachelor-Student)
Riccardo Pitzschler (Bachelor-Student)
Elisa Kinski (Diploma-Student)