Kontakt

Dr. Friedrich-Alexan­der Ludwig

Wissen­schaftlicher Mitarbei­ter / Radiochemie
Experimentelle Neuroonkologische Radiopharmazie
f.ludwigAthzdr.de
Tel.: +49 351 260 4617
+49 351 260 4624

Prof. Dr. Andreas Maurer

Lei­ter Experimentelle Neuroonkologische Radiopharmazie
a.maurerAthzdr.de
Tel.: +49 351 260 4610

Development of PSMA ligands for the diagnosis and treatment of prostate cancer


Prostate cancer is the second most commonly occurring cancer in men and the fourth most common cancer overall, with around 1.4 million new cases in 2020. The prostate-specific membrane antigen (PSMA) is known as a marker for prostate cancer as well as other solid tumors. Over the past 15 years several 18F-PSMA PET ligands have already been developed for prostate imaging. However, 99mTc remains a popular radiometal for SPECT imaging due to its longer half-life and availability from 99Mo/99mTc generators, particularly in outpatient imaging centers.

In collaboration with various departments of the Institute of Radiopharmaceutical Cancer Research and ABX GmbH, Radeberg, a series of PSMA-binding 99mTc-radioligands was synthesized and evaluated preclinically. Among the radioligands, which contain the PSMA binding motif Glu-urea-Lys, a varying linker and a bisaminothiol (BAT)-type N2S2 chelator, [99mTc]TcO-ABX474 (PSMA: Kd= 7.2 ± 1.7 nM) exhibited the most favorable properties. In particular, SPECT studies in LNCaP xenograft mice revealed higher tumor-to-background ratios  compared to the reference compound [99mTc]Tc-PSMA-I&S between 1 and 4 hours after injection and demonstrated a similar tumor visualization compared to PET/CT imaging with [68Ga]Ga-PSMA-11. Thus, [99mTc]TcO-ABX474 is still further characterized with regard to its chemical and biological properties. The translational potential of [99mTc]TcO-ABX474 as a SPECT imaging agent for prostate cancer has already been evaluated in a first-in-human study.

Beside the Department of Experimental Neurooncological Radiopharmacy, the following departments of the Institute of Radiopharmaceutical Cancer Research are involved:

  • Dept. Radiopharmaceutical and Chemical Biology

  • Dept. Medicinal Radiochemistry

  • Dept. Targetry, Target Chemistry and Radiopharmacy

  • Dept. Radioimmunology

Partners

  • ABX advanced biochemical compounds GmbH, Radeberg

  • University Hospital Muenster, Department of Nuclear Medicine, Muenster (Prof. Kambiz Rahbar)

  • University Hospital Carl Gustav Carus, Department of Nuclear Medicine, Dresden (PD Dr. Robert Freudenberg)

  • Hochschule Zittau/Görlitz, Fakultät für Natur- und Umweltwissenschaften (Prof. Jan Mollitor)

Financial Support

EFRE (European Regional Development Fund) together with the Free State of Saxony

  

Publications

  • Lis, C.; Ludwig, F.-A.; Fischer, S.; Ullrich, M.; Lankau, H.-J.; Sihver, W.; Gündel, D.; Joseph, D.; Meyer, C.; Kopka, K.; Pietzsch, J.; Brust, P.; Hoepping, A. Development of [99mTc]TcO-ABX474: Design, Synthesis and biological Evaluation of PSMA-binding Technetium-99m radioligands for SPECT Imaging of Prostate Cancer. Journal of Medicinal Chemistry 2024 (submitted)
  • Rahbar, K.; Wagner, S.; Schaeg, F.; Ventura, D.; Lis, C.; Schäfers, M.; Ludwig, F.-A.; Fischer, S.; Ullrich, M.; Sihver, W.; Kopka, K.; Hoepping, A. First Experiences with the new 99mTc labelled PSMA ligand [99mTc]TcO-ABX474 in Patients with Advanced Prostate Cancer Prior to PSMA targeted Radioligand Therapy. Journal of Nuclear Medicine 2024, 65, supplement 2, 241711
  • Ludwig, F.-A.; Lis, C.; Ullrich, M.; Lankau, H.-J.; Sihver, W.; Joseph, D.; Eiselt, E.; Meyer, C.; Gündel, D.; Deuther-Conrad, W.; Brust, P.; Donat, C. K.; Bachmann, M.; Pietzsch, H.-J.; Pietzsch, J.; Fischer, S.; Kopka, K.; Hoepping, A. Synthesis of novel PSMA ligands and preclinical evaluation of [99mTc]TcO-ABX474, a radioligand for SPECT imaging of prostate cancer. Nuclear Medicine and Biology 2022, 114-115, S3