Dr
Matthias Miederer
(Universitätsmedizin Mainz, Germany)
Radioimmunotherapy (RIT) of disseminated diseases in which individual cells or cell clusters are remaining requires a radionuclide that is capable of sterilizing individual cells with minimal radiotoxicity to surrounding healthy tissue. α particles exhibit high linear energy transfer and very short range in tissue, making them ideal for single-cell killing. 149Tb is a radiolanthanide that emits α particles with only 28 µm range in tissue. Feasibility and potential advantages of 149Tb over other radioisotopes in RIT have been studied in preclinical experiments using different monoclonal antibodies targeting leukemia, lymphoma and gastric cancer.
149Tb was produced at ISOLDE-CERN by on-line mass separation of spallation products released from a Ta target irradiated with 1 GeV protons. The monoclonal antibodies HuM195, Rituximab and d9ECad were conjugated with CHX-A-DTPA and labeled with 149Tb with specific activities of 0.1-1.1 GBq/mg.
In vivo capability of treating disseminated cancer was investigated using a disseminated lymphoma mouse model. 149Tb RIT with 5.5 MBq labeled Rituximab 2 days after an intravenous graft of lymphoma cells resulted in tumor free survival for >120 days in 89% of treated animals. In contrast, all control mice developed lymphoma disease.
There are many unsolved clinical situations in oncology, where α emitters are hoped to serve as therapeutic breakthrough to improve survival of cancer patients, e.g. disseminated single cell disease like leukemia, adjuvant treatment for circulating or loco-regionally remaining cells in solid tumors or treatment of minimal residual disease in lymphoma. Our experiments with 149Tb produced at CERN demonstrate this α emitter’s potential to overcome limitations of other radioisotopes in selected clinical settings.
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Langenbeckstrasse 1, 55131 Mainz
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Universitätsmedizin Mainz, Ger
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Curriculum vitae Dr. med. Matthias Miederer, DOB 30.10.1975
Klinik für Nuklearmedizin der Universitätsmedizin Mainz, Langenbeckstrasse 1, 55131 Mainz, phone: +40 6131 176516 email: miederer@nuklear.klinik.uni-mainz.de
1996 – 1998 school of medicine University of Hamburg, Germany
1998 - 2002 school of medicine, Technische Universität München, Germany
1999 - 2002 Technische Universität München, department of nuclear
medicine: biological experiments with alpha emitting isotopes (Dr. med.)
2002 – 2003 Sloan Kettering Institute in New York, research fellow
preclinical development on Actinium-225 therapy
2003 - 2004 Charité, Berlin, postgraduate medical training
2004 – 2009 Technische Universität München, department of nuclear
medicine (Prof. Dr. Schwaiger), nuclear medicine training
Since 2009 leading senior physician, department of nuclear medicine,
Mainz, Germany
Dr
Matthias Miederer
(Universitätsmedizin Mainz, Germany)
Prof.
Gerd-Jürgen Beyer
(Isotope Technologies Dresden GmbH,Dresden, Germany)
Dr
Josef Comor
(Vinca Institute of Nuclear Sciences, Belgrade, Serbia)
Dr
Sanja Vranjes-Duric
(Vinca Institute of Nuclear Sciences, Belgrade, Serbia)
