2. Academic Validation
  3. Development of [99mTc]TcO-ABX474: Design, Synthesis, and Biological Evaluation of PSMA-Binding Technetium-99m Radioligands for SPECT Imaging of Prostate Cancer

Development of [99mTc]TcO-ABX474: Design, Synthesis, and Biological Evaluation of PSMA-Binding Technetium-99m Radioligands for SPECT Imaging of Prostate Cancer

  • J Med Chem. 2025 Apr 10;68(7):7213-7231. doi: 10.1021/acs.jmedchem.4c02767.
Christian Lis 1,  Friedrich-Alexander Ludwig 2,  Steffen Fischer 2,  Martin Ullrich 2,  Hans-Joachim Lankau 1,  Wiebke Sihver 2,  Daniel Gündel 2,  Desna Joseph 1,  Christoph Meyer 1,  Klaus Kopka 2 3 4 5,  Jens Pietzsch 2 3,  Peter Brust 2 6,  Alexander Hoepping 1
Affiliations

Affiliations

  • 1 ABX Advanced Biochemical Compounds GmbH, Heinrich-Gläser-Straße 10-14, 01454 Radeberg, Germany.
  • 2 Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Bautzner Landstraße 400, 01328 Dresden, Germany.
  • 3 School of Science, Faculty of Chemistry and Food Chemistry, Technische Universität Dresden, Mommsenstraße 4, 01069 Dresden, Germany.
  • 4 German Cancer Consortium (DKTK), Partner Site Dresden, 01307 Dresden, Germany.
  • 5 National Center for Tumor Diseases (NCT), Partner Site Dresden, University Cancer Center (UCC), 01307 Dresden, Germany.
  • 6 University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23562 Lübeck, Germany.
PMID: 40135799 DOI: 10.1021/acs.jmedchem.4c02767
Abstract

A current global limitation to the timely and equitable patient access to PSMA-based therapies for prostate Cancer (PCa) is the insufficient PET capacity for pretreatment imaging. However, the extensive global availability of SPECT cameras renders this imaging technology as an attractive alternative. The lack of regulatory approved PSMA radioligands for SPECT imaging of PCa prompted us to design new 99mTc-labeled radioligands with a fast pharmacokinetic profile by harnessing proven complexation of the [99mTc][TcO]3+ core by a bis(aminoethanethiol) chelator. Six 99mTc-labeled PSMA radioligands were synthesized and biologically characterized in cell-based assays and by SPECT imaging in LNCaP tumor-bearing mice. From this series, [99mTc]TcO-5 ([99mTc]TcO-ABX474, Kd(PSMA) = 6.1 ± 1.7 nM) displayed the most advantageous properties for SPECT imaging of PCa: high and fast tumor uptake accompanied by rapid clearance from nontarget tissues, leading to faster pharmacokinetics than observed for the reference [99mTc]Tc-PSMA-I&S. Furthermore, [99mTc]TcO-5 performed similar to the established PSMA-PET radioligand [68Ga]Ga-PSMA-11.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-173476
    PSMA抑制剂
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