Division of Radiopharmaceutical Chemistry
Prof. Dr. rer. nat. Klaus Kopka
The Division Radiopharmaceutical Chemistry designs targeted radiotracers for the molecular imaging and diagnosis of cancer by means of positron emission tomography (PET) and by the en-vogue hybrid technologies PET/CT and PET/MRT, which are used for the highly sensitive non-invasive imaging of biological processes at the molecular level. The focus is the visualisation of rather early disease states or early inspection of treatment response after chemotherapy, radiation therapy or targeted internal radiation therapy (radioendotherapy) in vivo. One main task is thus the development of novel PET radiopharmaceuticals targeting receptors, transport systems and enzymes relevant in early tumorigenesis and tumor progression to establish a tool for improving the clinical management of patients suffering from tumors, thereby tending to the identification or even the prevention of tumor dissemination.
Radiopharmaceutical Chemistry reverts to interdisciplinary fields, such as nuclear chemistry using cyclotrons (figure) and radionuclide generators. Sub-fields such as labelling chemistry, medicinal chemistry, organic and solid-phase chemistry are further required. To fulfil the translation of new PET tracers into the clinical scenario special laboratory environments are needed to set up Good Manufacturing Practice (GMP)-compliant automated radiosyntheses in highly sophisticated clean rooms which comply with radiation protection and also with the pharmaceuticals act.
Notably, the Division Radiopharmaceutical Chemistry will focus on the development of peptidyl and non-peptidyl tracers, i.a. radiolabelled with PET-compatible radionuclides, such as F-18, Ga-68 and others, targeting enzymes such as matrix metalloproteinases (MMPs) and the prostate-specific membrane antigen (PSMA) as well as membrane-associated receptors and biological targets playing key roles in neoangiogenesis. The tailor-made diagnostic tracers should be designed in such a way that they can also be used as therapeutic pharmaceuticals which bear corresponding particle emitters such as Y-90, Lu-177 and others (i.e. “in vivo theranostic approach”, already established for Ga-68- and Lu-177-DOTATOC). We speculate that the non-invasive in vivo visualisation of these biological targets by those target-affine radiotracers will elucidate still unsolved clinical oncological questions, in any case for the patient’s benefit.
Looking at aforementioned aspects the Division Radiopharmaceutical Chemistry fits elegantly into the context of the research program Imaging and Radiooncology (FSE). The motivation is to directly link basic research expertise to the GMP-compliant production of corresponding PET tracers for clinical research, as is the case for [18F]FDG, [18F]FLT, [18F]FET, Na[18F]F, [68Ga]Ga-DOTATOC and [68Ga]Ga-PSMA, to support cancer research at DKFZ. In this connexion a close cooperation with the clinical cooperation unit Nuclear Medicine is indispensable.
Eder M, Löhr T, Bauder-Wüst U, Reber M, Mier W, Schäfer M, Haberkorn U, Eisenhut M. Pharmacokinetic Properties of Peptidic Radiopharmaceuticals: Reduced Uptake of (EH)3-Conjugates in Important Organs. J Nucl Med 2013, 54, 1327-1330.
Hugenberg V, Riemann B, Hermann S, Schober O, Schäfers M, Szardenings AK, Lebedev A, Gangadharmath U, Kolb H, Walsh J, Zhang W, Kopka K, Wagner S. Inverse 1,2,3-triazole-1-yl-ethyl substituted hydroxamates as highly potent matrix metalloproteinase inhibitors: (Radio)synthesis, in vitro and first in vivo evaluation. J Med Chem 2013, 56, 6858-6870.
Waldmann C, Schober O, Haufe G, Kopka K. A Closer Look at the Bromine Lithium Exchange with tert Butyllithium in an Aryl Sulfonamide Synthesis. Org Lett 2013, 15, 2954-2957.
Schrigten D, Breyholz HJ, Wagner S, Hermann S, Schober O, Schäfers M, Haufe G, Kopka K. A New Generation of Radiofluorinated Pyrimidine-2,4,6-triones as MMP-targeted Radiotracers for Positron Emission Tomography. J Med Chem 2012, 55, 223-232.