The Use of Glycine-Containing Peptide-Based Chelators for Labeling with 99mTc Improves the Imaging Properties of EpCAM-Targeting Designed Ankyrin Repeat Ec1; Molecular Pharmaceutics; Vol. 23, iss. 4

The Use of Glycine-Containing Peptide-Based Chelators for Labeling with 99mTc Improves the Imaging Properties of EpCAM-Targeting Designed Ankyrin Repeat Ec1; Molecular Pharmaceutics; Vol. 23, iss. 4

Bibliographic Details
Parent link:Molecular Pharmaceutics.— .— Washington: ACS Publications
Vol. 23, iss. 4.— 2026.— P. 2469–2480
Other Authors: Deev S. M. Sergey Mikhaylovich, Fominykh A. S. Anastasiya Sergeevna, Varvashenya R. N. Ruslan Nikolaevich, Yanovich G. Gleb, Bodenko V. V. Vitalina Vasiljevna, Plotnikov E. V. Evgeny Vladimirovich, Tretyakova (Tretjyakova) M. S. Maria Sergeevna, Eskova D. D. Darjya Dmitrievna, Zelchan (Zeltchan) R. V. Roman Vladimirovich, Shulga (Schulga) A. A. Aleksey Anatolievich, Konovalova E. V. Elena Valerjevna, Ziganshin R. Rustam, Orlova A. M. Anna Markovna, Belousov M. V. Mikhail Valerievich, Tolmachev V. M. Vladimir Maksimilianovich, Larkina M. S. Mariya Sergeevna
Summary:Title screen
Noninvasive radionuclide imaging of epithelial cell adhesion molecule (EpCAM) expression in lung, ovarian, breast, kidney, and other cancers can stratify patients for EpCAM-targeted therapy. The constructed scaffold proteins, designed ankyrin repeat proteins (DARPins), are highly specific high-affinity probes for radionuclide imaging. A clinical study demonstrated that the anti-EpCAM DARPin [99mTc]Tc-(HE)3-Ec1 showed precise EpCAM imaging at 2, 4, and 6 h after injection in patients with nonsmall cell lung cancer. However, a noticeable accumulation in healthy organs has prompted the development of new Ec1-based agents with improved biodistribution properties. In addition, it would be desirable to substitute a labor-intensive labeling procedure. The purpose of this study was to test the hypothesis that the use of Gly-Gly-Gly-Cys (G3C) or Glu-Glu-Glu-Cys (E3C) peptide chelators placed at the C-terminus of DARPin for labeling with 99mTc (V) could improve the image contrast and biodistribution of Ec1. The radiochemical yield of the new variants exceeded 95%. The labeled proteins specifically bound to human EpCAM-expressing cancer cell lines with affinities of 8–10 nM. The biodistribution of [99mTc]Tc-Ec1-G3C and [99mTc]Tc-Ec1-E3C in mice was compared with the biodistribution of clinically tested [99mTc]Tc-(HE)3-Ec1 in a Nu/j mouse model with SKOV-3 xenografts. The new variants specifically accumulate in human xenografts with EpCAM expression. The accumulation of new variants in healthy organs (liver, salivary glands, spleen, and stomach) was reduced compared to [99mTc]Tc-(HE)3-Ec1. [99mTc]Tc-Ec1-G3C provided the best imaging contrast and is suitable for clinical testing
AM_Agreement
Language:English
Published: 2026
Subjects:
труды учёных ТПУ
электронный ресурс
EpCAM
radionuclide molecular imaging
DARPin Ec1
engineered scaffold proteins
ESP
Online Access:https://doi.org/10.1021/acs.molpharmaceut.5c01498
Format: Electronic Book Chapter
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=686119

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