Radiopharmaceutical Chemistry

Division of Radiopharmaceutical Chemistry

Prof. Dr. rer. nat. Klaus Kopka

Negative ion 32 MeV cyclotron MC32NI at DKFZ for the production of radionuclides.
© dkfz.de

The Division of Radiopharmaceutical Chemistry designs targeted radiotracers for molecular imaging and diagnosis of cancer by means of the en-vogue hybrid technologies PET/CT and PET/MRI, which are used for highly sensitive non-invasive imaging of biological processes at a molecular und submolecular level. The focus is on the visualization of rather early disease states or early inspection of treatment response after chemotherapy, radiation therapy or targeted internal radiation therapy (i.e. endoradiotherapy or radioligand therapy (RLT)) 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 cancer. On that account, we aim to advance the identification and the prevention of tumor dissemination or in case of tumor dissemination to offer optimized theragnostic treatment options for the patients by means of endoradiotherapy. The currently most prominent in vivo theragnostic success story is the targeted RLT of prostate cancer by means of prostate-specific membrane antigen (PSMA) radioligands. Coworkers of the Div. of Radiopharmaceutical Chemistry recently discovered the novel radiopharmaceutical drug PSMA-617 (see Benešová M et al.). Radiolabelled with the beta emitter lutetium-177 PSMA-617 is promising for the treatment of patients with metastatic castration resistant prostate cancer (mCRPC), which is difficult to control and linked to poor prognosis. Treatment with the theragnostic agent PSMA-617 could offer more effective and sensitive visualization, better staging and significantly higher therapeutic potential. To be clear, other PSMA-based theragnostic agents have also been established in the clinical research area, but obviously the variant PSMA-617 seems to be one of the most promising theragnostic PSMA radioligands so far. This new radiopharmaceutical drug, i.e. PSMA-617, shows strong binding to the protein PSMA and is readily and safely taken up by malignant PSMA-positive tumors. PSMA-617 could represent a watershed moment for prostate cancer theragnostics. For this research, scientists of the Div. of Radiopharmaceutical Chemistry together with the Dept. of Nuclear Medicine of the Heidelberg University Hospital have been awarded with the Henry N. Wagner, Jr., MD, Image of the Year Award 2015 of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), Baltimore, Maryland (USA).

FUTURE OUTLOOK
This highly distinguished award in the field of Radiopharmaceutical Chemistry and Nuclear Medicine released a follow-up project in the Div. of Radiopharmaceutical Chemistry to identify, in addition to recent efforts in the U.S., a fluorine-18 labelled theragnostic analogue for PET/CT and PET/MRI prestaging of patients considered for PSMA-617 endoradiotherapy. Due to the preferable physical characteristics of the positron emitter fluorine-18 for PET-imaging and the possibility of large scale production in our cyclotron-based GMP-compliant production environment a radiofluorinated diagnostic version of PSMA-617 is also a promising alternative to the famous diagnostic Gallium-68 labelled PSMA-PET radioligand [68Ga]Ga-PSMA-11, also recently invented in the Div. of Radiopharmaceutical Chemistry (under supervision of Prof. Dr. Michael Eisenhut).

Notably, the Div. of Radiopharmaceutical Chemistry will hence still focus on the development of peptidomimetic theragnostic PSMA-targeted radiotracers, the fluorine-18, copper-64 and gallium-68 labelled variants functioning as PSMA-PET tracers, the yttrium-90, lutetium-177 and actinium-225 labelled variants functioning as therapeutic radiopharmaceuticals. The clinical translation of this research project can only be realized by tight cooperation with the CCU Nuclear Medicine and the Dept. of Nuclear Medicine of the Heidelberg University Hospital (concerning first-in-man transfer, Prof. Dr. Uwe Haberkorn) and the Institute of Transuranium Elements (ITU) Karlsruhe (concerning supply of actinium-225, Prof. Dr. Alfred Morgenstern).

Last but not least, the ongoing DKTK initiative of the multicenter clinical trial (Phases 1 and 2) ”[68Ga]Ga-PSMA-11 in high-risk prostate cancer” (Sponsor DKFZ Heidelberg) is one of the “side-entrance” endeavors during the first DKTK period (since 10/2013). The participating decentralized radiopharmacies (11 centers within D-A-CH region) are coordinated by the Div. of Radiopharmaceutical Chemistry. The clinical planning of this unique figurehead multicenter clinical trial with this promising PET tracer is taken over by the Dept. of Nuclear Medicine of Heidelberg University Hospital. The clinical value of [68Ga]Ga-PSMA-11 was already discovered in 2011 by the Heidelberg group so that already in late 2013 the DKTK-driven consortium could be founded.

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.

Contact

Prof. Dr. rer. nat. Klaus Kopka
Radiopharmaceutical Chemistry (E030)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 2432

Selected Publications

  • Benešová, M., Bauder-Wüst, U., Schäfer, M., Klika, K.D., Mier, W., Haberkorn, U., Kopka, K., Eder, M.: Linker Modification Strategies To Control the Prostate-Specific Membrane Antigen (PSMA)-Targeting and Pharmacokinetic Properties of DOTA-Conjugated PSMA Inhibitors. J Med Chem. 59(5), 1761-75, 2016.
  • Liolios, C., Schäfer, M., Haberkorn, U., Eder, M., Kopka, K.: Novel Bispecific PSMA/GRPr Targeting Radioligands with Optimized Pharmacokinetics for Improved PET Imaging of Prostate Cancer. Bioconjug Chem. 27(3), 737-51, 2016.
  • Haberkorn U, Kopka K, Hadaschik B. Positron Emission Tomography-computed Tomography with Prostate-specific Membrane Antigen Ligands as a Promising Tool for Imaging of Prostate Cancer. Eur Urol 2016; 69(3): 397-399. doi: 10.1016/j.eururo.2015.08.059.
  • Haberkorn U, Eder M, Kopka K, Babich JW, Eisenhut M. New Strategies in Prostate Cancer: Prostate-Specific Membrane Antigen (PSMA) Ligands for Diagnosis and Therapy. Clin Cancer Res 2016; 22(1): 9-15. doi: 10.1158/1078-0432.CCR-15-0820.
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