Preclinical Characterization of the 177Lu-Labeled Prostate Stem Cell Antigen (PSCA)-Specific Monoclonal Antibody 7F5

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Franziska Striese - , School of Science, Chair of Bioinorganic and Radiopharmaceutical Chemistry, Helmholtz-Zentrum Dresden-Rossendorf, TUD Dresden University of Technology (Author)
  • Christin Neuber - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Sandy Gräßel - , Helmholtz-Zentrum Dresden-Rossendorf, TUD Dresden University of Technology (Author)
  • Claudia Arndt - , Helmholtz-Zentrum Dresden-Rossendorf, University Cancer Center (UCC) (Author)
  • Martin Ullrich - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Jörg Steinbach - , School of Science, Chair of Bioinorganic and Radiopharmaceutical Chemistry, Helmholtz-Zentrum Dresden-Rossendorf, TUD Dresden University of Technology (Author)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf, TUD Dresden University of Technology (Author)
  • Ralf Bergmann - , Helmholtz-Zentrum Dresden-Rossendorf, Semmelweis University (Author)
  • Hans Jürgen Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Wiebke Sihver - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Marcus Frenz - , Provadis School of International Management and Technology AG (Author)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf, University Cancer Center (UCC) (Author)
  • Michael P. Bachmann - , University Cancer Centre, Helmholtz-Zentrum Dresden-Rossendorf, German Cancer Research Center (DKFZ) (Author)

Abstract

Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A″-DTPA and subsequently radiolabeled it with the theranostic radionuclide 177Lu. The resulting radiolabeled mAb ([177Lu]Lu-CHX-A″-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [177Lu]Lu-CHX-A″-DTPA-7F5. Consequently, [177Lu]Lu-CHX-A″-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy.

Details

Original languageEnglish
Article number9420
JournalInternational journal of molecular sciences
Volume24
Issue number11
Publication statusPublished - Jun 2023
Peer-reviewedYes

External IDs

PubMed 37298374

Keywords

Sustainable Development Goals

Keywords

  • CHX-A″-DTPA, Lu-labeled antibody, prostate cancer, prostate stem cell antigen, Carcinoma/drug therapy, Antibodies, Monoclonal/therapeutic use, Male, Tissue Distribution, Stem Cells, Animals, Lutetium/chemistry, Cell Line, Tumor, Mice, Pentetic Acid/chemistry, Prostate