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Related Experiment Video

Updated: Jun 16, 2025

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Selection of the optimal chelator for labeling of DARPin Ec1 with gallium-68 for PET imaging of EpCAM expression.

Anzhelika Vorobyeva1, Moeen-Ud Din1, Alexey Schulga2

  • 1Department of Immunology, Genetics and Pathology, Uppsala University, 751 85, Uppsala, Sweden.

EJNMMI Radiopharmacy and Chemistry
|May 30, 2025
PubMed
Summary

The study found that Gallium-68 labeled Ec1-NOTA is the best choice for PET imaging of Epithelial cell adhesion molecule (EpCAM) expression, offering superior biodistribution and tumor-to-blood ratios compared to other variants.

Keywords:
68GaDesigned ankyrin repeat proteins (DARPin)Epithelial cell adhesion molecule (EpCAM)PET imagingSKOV-3 xenograft

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Area of Science:

  • Biomedical imaging
  • Radiopharmaceutical chemistry
  • Molecular imaging

Background:

  • Epithelial cell adhesion molecule (EpCAM) is a key biomarker overexpressed in various cancers.
  • Designed ankyrin repeat protein (DARPin) Ec1 exhibits high affinity for EpCAM.
  • Radiolabeled Ec1 holds potential for companion diagnostics in personalized cancer therapy.

Purpose of the Study:

  • To evaluate the impact of different radiometal-chelator complexes on the biodistribution and imaging contrast of 68Ga-labeled Ec1.
  • To compare 68Ga-labeled Ec1 conjugated with NOTA and NODAGA against a DOTA-conjugated variant.

Main Methods:

  • Conjugation of NOTA and NODAGA chelators to the C-terminus of DARPin Ec1.
  • Radiolabeling of Ec1 variants with 68Ga.
  • In vitro and in vivo assessment of binding affinity, targeting specificity, and biodistribution in EpCAM-positive xenografts.
  • Comparison of radiochemical yield and label stability.

Main Results:

  • All 68Ga-labeled Ec1 variants demonstrated high affinity and specific binding to EpCAM-expressing cells.
  • NOTA and NODAGA chelators resulted in higher radiochemical yields and improved label stability compared to DOTA.
  • [68Ga]Ga-Ec1-NOTA exhibited lower uptake in normal organs, particularly the liver, while maintaining tumor uptake.
  • The [68Ga]Ga-Ec1-NOTA conjugate achieved the highest tumor-to-blood ratio.

Conclusions:

  • 68Ga-labeled Ec1-NOTA is the optimal radioconjugate for Positron Emission Tomography (PET) imaging of EpCAM expression.
  • The choice of chelator significantly influences the pharmacokinetic properties and imaging performance of EpCAM-targeting radiotracers.
  • [68Ga]Ga-Ec1-NOTA offers improved imaging contrast and reduced off-target accumulation for EpCAM-positive tumor detection.