Evaluation of a Pretargeting Strategy for Molecular Imaging of the Prostate Stem Cell Antigen with a Single Chain Antibody

Lena Tienken, Natascha Drude*, Isabell Schau, Oliver H. Winz, Achim Temme, Elmar Weinhold, Felix M. Mottaghy, Agnieszka Morgenroth

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

In pretargeted radio-immunotherapy, the gradual administration of a non-radioactive tumor antigen-addressing antibody-construct and the subsequent application of a radioactive labeled, low molecular weight substance enable a highly effective and selective targeting of tumor tissue. We evaluated this concept in prostate stem cell antigen (PSCA)-positive cancers using the antigen-specific, biotinylated single chain antibody scFv(AM1)-P-BAP conjugated with tetrameric neutravidin. To visualize the systemic biodistribution, a radiolabeled biotin was injected to interact with scFv(AM1)-P-BAP/neutravidin conjugate. Biotin derivatives conjugated with different chelators for complexation of radioactive metal ions and a polyethylene glycol linker (n = 45) were successfully synthesized and evaluated in vitro and in a mouse xenograft model. In vivo, the scFv(AM1)-P-BAP showed highly PSCA-specific tumor retention with a PSCA(+) tumor/PSCA-tumor accumulation ratio of ten. PEGylation of radiolabeled biotin resulted in lower liver uptake improving the tumor to background ratio.
Original languageEnglish
Article number3755
Number of pages9
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 28 Feb 2018

Keywords

  • BIOTIN-BINDING
  • IN-VIVO
  • RADIOIMMUNOTHERAPY
  • THERAPY
  • AVIDIN
  • STREPTAVIDIN
  • CANCER
  • NEUTRAVIDIN
  • XENOGRAFTS
  • PEGYLATION

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