Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1.

Abstract

Efficient treatment of disseminated triple-negative breast cancer (TNBC) remains an unmet clinical need. The epithelial cell adhesion molecule (EpCAM) is often overexpressed on the surface of TNBC cells, which makes EpCAM a potential therapeutic target. Radionuclide molecular imaging of EpCAM expression might permit selection of patients for EpCAM-targeting therapies. In this study, we evaluated a scaffold protein, designed ankyrin repeat protein (DARPin) Ec1, for imaging of EpCAM in TNBC. DARPin Ec1 was labeled with a non-residualizing [125I]I-para-iodobenzoate (PIB) label and a residualizing [99mTc]Tc(CO)3 label. Both imaging probes retained high binding specificity and affinity to EpCAM-expressing MDA-MB-468 TNBC cells after labeling. Internalization studies showed that Ec1 was retained on the surface of MDA-MB-468 cells to a high degree up to 24 h. Biodistribution in Balb/c nu/nu mice bearing MDA-MB-468 xenografts demonstrated specific uptake of both [125I]I-PIB-Ec1 and [99mTc]Tc(CO)3-Ec1 in TNBC tumors. [125I]I-PIB-Ec1 had appreciably lower uptake in normal organs compared with [99mTc]Tc(CO)3-Ec1, which resulted in significantly (p < 0.05) higher tumor-to-organ ratios. The biodistribution data were confirmed by micro-Single-Photon Emission Computed Tomography/Computed Tomography (microSPECT/CT) imaging. In conclusion, an indirectly radioiodinated Ec1 is the preferable probe for imaging of EpCAM in TNBC.

• Authors: Anzhelika Vorobyeva, Ekaterina Bezverkhniaia, Elena Konovalova, Alexey Schulga, Javad Garousi, Olga Vorontsova, Ayman Abouzayed, Anna Orlova, Sergey Deyev, Vladimir Tolmachev
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 20 (Oct 14 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 33066684 (Publication Type: Journal Article)

Chemical References

• 4-Iodobenzoic acid
• ANKRD23 protein, human
• EPCAM protein, human
• Epithelial Cell Adhesion Molecule
• Iodine Radioisotopes
• Iodobenzoates
• Molecular Probes
• Muscle Proteins
• Nuclear Proteins
• Radiopharmaceuticals
• Technetium-99
• Technetium
• 2-iodobenzoic acid
• Iodine-125

Topics

• Animals
• Cell Line, Tumor
• Epithelial Cell Adhesion Molecule (analysis, metabolism)
• Female
• Humans
• Iodine Radioisotopes (chemistry, pharmacokinetics)
• Iodobenzoates (chemistry)
• Mice, Inbred BALB C
• Molecular Imaging (methods)
• Molecular Probes (chemistry, pharmacokinetics)
• Muscle Proteins (chemistry)
• Nuclear Proteins (chemistry)
• Radiopharmaceuticals (chemistry, pharmacokinetics)
• Technetium
• Tissue Distribution
• Tomography, Emission-Computed, Single-Photon (methods)
• Triple Negative Breast Neoplasms (metabolism)
• Xenograft Model Antitumor Assays