Contact

Dr. Magali Toussaint

Research Associate / Biology
Experimental Neurooncological Radiopharmacy
m.toussaintAthzdr.de
Phone: +49 351 260 4616

Dr. Winnie Deuther-Conrad

Research Associate
Experimental Neurooncological Radiopharmacy
w.deuther-conradAthzdr.de
Phone: +49 351 260 4613

Dr. Barbara Wenzel

Research Associate / Radiochemistry
Experimental Neurooncological Radiopharmacy
b.wenzelAthzdr.de
Phone: +49 351 260 4637
+49 351 260 4625

Development of PET radioligands for imaging of mutant isocitrate dehydrogenase 1 (mIDH1) in brain tumours


Isocitrate dehydrogenase 1 (IDH1) R132H mutations are found in approximately 80% of astrocytomas and oligodendrogliomas, incurable primary malignant brain tumours. Clinical data show that IDH1R132H mutations in gliomas correlate with favourable survival. Ongoing studies are also testing the effect of targeted therapies in IDH-mutant gliomas, using either mutation-specific small molecule inhibitors or vaccination. The IDH mutation status is currently determined using immunohistochemical analysis of tumour tissue obtained from surgical tumour resection or biopsy.
To develop a non-invasive method for detecting the presence of mutant IDH1 (mIDH1) in gliomas, we are using medicinal chemistry to modify pharmacologically active small molecule mIDH1 inhibitors to generate radiofluorinated mIDH1 ligands that can be used for positron emission tomography (PET). We combine in vitro and in vivo techniques to examine the potential of the new 18F-labelled mIDH1 ligands as imaging agents.
We are part of an international research consortium formed by clinicians, research labs and a pharmaceutical company.

          
 
Structure of the 18F-labelled version of the mIDH inhibitor ([18F]AG-120; left); PET/MR images of the brain of an IDH1- (middle) and an IDH1R132H-expressing glioblastoma rat (right) 40-60  min after intravenous injection of [18F]AG-120. From Lai et al., EJNMMI 2024

Partners

  • Prof. Aurélie Maisonial-Besset, Université Clermont Auvergne, UFR de Pharmacie, Clermont-Ferrand, Frankreich

  • Prof. Tareq Juratli, Prof. Klaus - D. Schaser, Dr. Anne Weidlich, Dr. Hagen Fritzsche, University Hospital Carl Gustav Carus at the Technical University of Dresden, Clinic for Neurosurgery, Dresden, Germany

  • Dr. Sabine Schulze, Medical Faculty of Technical University Dresden, Germany
  • Prof. Christopher Schofield, Department of Chemistry, University of Oxford, UK

  • Dr. Sebastian Greiser, Experimental Imaging Unit, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

  • Dr. Thu Hang Lai, Pharmaceutical Development, ROTOP Pharmaka GmbH, Dresden, Germany

  • Dr. Jacqueline Kessler, Department of Radiotherapy, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

  • Prof. Dirk Vordermark, Department of Radiotherapy, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

Financial Support

  • PET-IDH: Development of PET radioligands for imaging of mutant isocitrate dehydrogenase 1 (mIDH1) in solid tumours (Agence Nationale de la Recherche and Deutsche Forschunsgemeinschaft), 09/2024 – 08/2027

  • IDH-PET 2: Nicht-invasive Bildgebung von Hirntumoren – Entwicklung eines Radiopharmakons zum Nachweis der Isocitrat-Dehydrogenase-Mutation in Gliomen (European Regional Development Fund (ERDF) and Sächsische Aufbaubank (SAB)), 07/2023 – 06/2026

  • IDH Exchange: Development of radioligands for imaging of mutant isocitrate dehydrogenase 1 in cancer (DAAD - Deutscher Akademischer Austauschdienst, PROCOPE), 01/2023 – 12/2024

  • IDH-PET: Entwicklung eines PET-Radiopharmakons für den nuklearmedizinischen Nachweis von Mutationen der Isocitrat-Dehydrogenase (IDH) im menschlichen Gliom (European Regional Development Fund (ERDF) and Sächsische Aufbaubank (SAB)), 07/2019 – 06/ 2022

                

   

Publications

  • Lai T., Wenzel B., Dukić-Stefanović S., Teodoro R.; Arnaud L., Maisonial-Besset A., Weber V., Moldovan R.-P., Meister S., Pietzsch J, Kopka K., Juratli T. A., Deuther-Conrad W. Toussaint M. Radiosynthesis and biological evaluation of [18F]AG-120 for PET imaging of the mutant isocitrate dehydrogenase 1 in glioma. Eur J Nucl Med Mol Imaging 51, 1085–1096 (2024). https://doi.org/10.1007/s00259-023-06515-7

  • Weber V, Arnaud L, Dukic-Stefanovic S, Wenzel B, Roux V, Chezal J-M, Lai T-H, Teodoro R, Kopka K, Miot-Noirault E, Deuther-Conrad W Maisonial-Besset, A. Novel Radioiodinated and Radiofluorinated Analogues of FT-2102 for SPECT or PET Imaging of mIDH1 Mutant Tumours. Molecules. 2022; 27(12):3766. https://doi.org/10.3390/molecules27123766