Projektbereiche - Übersicht

E030 Radiopharmazeutische Chem...

The Division of Radiopharmaceutical Chemistry is interested in the molecular imaging and early diagnosis of cancer using targeted radiotracers especially for positron emission tomography (PET) and for the nowadays existing hybrid technologies PET/CT and PET/MRI. The main task will be the development of novel PET radiopharmaceuticals addressing biological targets such as receptors and enzymes relevant in early tumorigenesis and tumor progression to establish a tool for finally improving the clinical management of patients suffering from tumors thereby tending to the identification or even the prevention of tumor dissemination.

During development of PET tracers Radiopharmaceutical Chemistry reverts to corresponding interdisciplinary and interfaculty fields starting with nuclear chemistry and with radionuclide production (using cyclotrons and radionuclide generator systems). In particular, sub-fields such as labeling chemistry, medicinal chemistry, organic, bioinorganic and solid-phase chemistry are required to realize the development of mentioned radiotracers from basic via preclinical research to clinical application. 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 (fully) automated radiosyntheses which are performed in highly sophisticated clean rooms which comply with radiation protection and at the same time with the EU-GMP regulations for radiopharmaceuticals.

Notably, the Division of Radiopharmaceutical Chemistry will focus on the development of peptidyl and non-peptidyl tracers, i.a. radiolabeled with the PET-compatible radionuclides, such as 18F, 68Ga, 64Cu, 44Sc, and others, targeting the prostate-specific membrane antigen (PSMA) enzyme, the class of matrix metalloproteinases (MMPs) as well as membrane-associated receptors and biological targets playing key roles in (neo)angiogenesis and response to therapy. 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 90Y, 177Lu, and others (i.e. “in vivo theranostic approach”, already established for Ga-68- and Lu-177-DOTATOC). We speculate that the noninvasive in vivo visualization of these carefully selected biological targets using corresponding target-affine PET tracers will elucidate still unsolved clinical oncological and neurooncological questions, in any case for the patient’s benefit.

By example PSMA is primarily restricted to the prostate and abundantly expressed at all stages of prostate tumor progression. PSMA is presented on the cell surface and it is not shed into the circulation. Therefore, PSMA can be considered as a promising target for specific prostate cancer imaging and radioendotherapy.

MMPs play a decisive role in tumor progression and tumor invasion and may function as a prognostic marker for tumor dissemination and at the same time as a target for therapy. Anyhow, the noninvasive imaging of MMP activity in vivo by means of PET/CT and PET/MRI will lead to the assessment of aggressive tumors.

The expression of the chemokine receptor CXCR4 in tumors is associated with tumor aggressiveness and poor prognosis for the patient due to its contribution to metastatic seeding. Therefore it is of high clinical interest to find a specific PET tracer for the imaging of CXCR4 expression in tumors.

Moreover the imaging of apoptosis using corresponding PET tracers may represent an approach in the long term. Activated executioner caspases have been suggested as biological target to in vivo visualize programmed type I cell death. This enzyme class or alternative biological targets relevant in early stages of apoptosis have to be identified to establish the feasibility to early and noninvasively monitor any successful therapy, such as immuno-, chemo- or radiation therapy.

Looking at aforementioned aspects the Division of 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 F-18-FDG, F-18-FLT, F-18-FET, Na F-18, Ga-68-DOTATOC, and Ga-68-PSMA-HBED-CC, to support cancer research at dkfz. In this connection a close cooperation with the clinical cooperation unit (CCU) Nuclear Medicine is indispensable.

In summary the translational research concept of the Division of Radiopharmaceutical Chemistry will balance innovative basic research on new targeted PET tracers and their application in man and thus will have great clinical impact on oncological patient management in the future.

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