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

Molecules

Anzhelika Vorobyeva¹  Vladimir Tolmachev¹  Olga Vorontsova¹  Javad Garousi¹  Ayman Abouzayed²  Elena Konovalova³  Sergey Deyev⁴  Alexey Schulga⁴  Ekaterina Bezverkhniaia⁴  Anna Orlova⁴ 

[1] Department of Immunology, Genetics and Pathology, Uppsala University, 751 85 Uppsala, Sweden;Department of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden;Molecular Immunology Laboratory, Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia;Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, National Research Tomsk Polytechnic University, 634 050 Tomsk, Russia;

关键词: EpCAM;    radionuclide;    molecular imaging;    SPECT;    iodine;    PIB;   

DOI  :  10.3390/molecules25204719

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown