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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Franziska Striese - , Bereich Mathematik und Naturwissenschaften, Professur für Bioanorganische und Radiopharmazeutische Chemie (gB/HZDR) (BC3), Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Autor:in)
  • Christin Neuber - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Sandy Gräßel - , Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Autor:in)
  • Claudia Arndt - , Helmholtz-Zentrum Dresden-Rossendorf, Universitäts KrebsCentrum Dresden (UCC) (Autor:in)
  • Martin Ullrich - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Jörg Steinbach - , Bereich Mathematik und Naturwissenschaften, Professur für Bioanorganische und Radiopharmazeutische Chemie (gB/HZDR) (BC3), Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Autor:in)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf, Technische Universität Dresden (Autor:in)
  • Ralf Bergmann - , Helmholtz-Zentrum Dresden-Rossendorf, Semmelweis University (Autor:in)
  • Hans Jürgen Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Wiebke Sihver - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Marcus Frenz - , Provadis School of International Management and Technology AG (Autor:in)
  • Anja Feldmann - , Helmholtz-Zentrum Dresden-Rossendorf, Universitäts KrebsCentrum Dresden (UCC) (Autor:in)
  • Michael P. Bachmann - , Universitäts KrebsCentrum Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummer9420
FachzeitschriftInternational journal of molecular sciences
Jahrgang24
Ausgabenummer11
PublikationsstatusVeröffentlicht - Juni 2023
Peer-Review-StatusJa

Externe IDs

PubMed 37298374

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • 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