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
| Parent link: | Molecular Pharmaceutics.— .— Washington: ACS Publications Vol. 23, iss. 4.— 2026.— P. 2469–2480 |
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| Other Authors: | , , , , , , , , , , , , , , , |
| 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
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| Subjects: | |
| 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 |
| 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 |
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| DOI: | 10.1021/acs.molpharmaceut.5c01498 |