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Biodistribution of the Bombesin Receptor-Targeted Radiopharmaceutical Precursor BBN/C1-C2 in a Prostate Cancer Model.

E A Beloborodov1, E V Iurova2, D R Dolgova3

  • 1Researcher, Laboratory of Research and Development of Peptide Drugs and Vaccines, S.P. Kapitsa Technological Research Institute; Ulyanovsk State University, 42 Leo Tolstoy St., Ulyanovsk, Russia, 432017.

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The novel BBN/C1-C2 molecule shows selective tumor binding and prolonged retention for up to 5 days in a prostate cancer model. This gastrin-releasing peptide receptor (GRPR) targeting agent demonstrates low uptake in normal organs, indicating potential for improved cancer diagnostics and therapy.

Keywords:
bombesinbombesin receptorknottinpeptide toxintargeted therapy

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Area of Science:

  • Biomedical research
  • Molecular imaging
  • Oncology

Background:

  • Gastrin-releasing peptide receptor (GRPR) is overexpressed in many solid cancers.
  • Current GRPR radiopharmaceuticals face challenges with normal organ uptake and drug stability.
  • There is a need for GRPR radioantagonists with enhanced tumor retention and reduced off-target accumulation.

Purpose of the Study:

  • To analyze the biodistribution and tumor accumulation dynamics of the BBN/C1-C2 molecule.
  • To evaluate the potential of BBN/C1-C2 as a GRPR-targeting agent for cancer applications.

Main Methods:

  • The study utilized a Cy7.5-labeled BBN/C1-C2 peptide, synthesized via solid-phase peptide synthesis.
  • Biodistribution was assessed in a mouse model (Nu/Nu) bearing GRPR-expressing prostate cancer (PC-3).
  • Real-time surface fluorescent imaging was employed on days 2 and 5 post-intravenous administration.

Main Results:

  • The BBN/C1-C2 molecule demonstrated selective binding and sustained retention on the tumor surface for up to 5 days.
  • Internalization into tumor cells was minimal, and accumulation in normal organs and tissues was low.
  • The molecule exhibited improved stability and bioavailability compared to existing GRPR ligands.

Conclusions:

  • The BBN/C1-C2 molecule shows promising characteristics for GRPR-targeted cancer diagnostics and therapy due to its selective tumor targeting and prolonged retention.
  • Further studies are required to address potential off-target effects related to the knottin scaffold's ion channel affinity before clinical application in radiotherapy.