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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| Další autoři: | , , , , , , , , , , , , , , , |
| Shrnutí: | 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 |
| Jazyk: | angličtina |
| Vydáno: |
2026
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| Témata: | |
| On-line přístup: | https://doi.org/10.1021/acs.molpharmaceut.5c01498 |
| Médium: | Elektronický zdroj Kapitola |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=686119 |
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| 200 | 1 | |a The Use of Glycine-Containing Peptide-Based Chelators for Labeling with 99mTc Improves the Imaging Properties of EpCAM-Targeting Designed Ankyrin Repeat Ec1 |f Sergey Deyev, Anastasia Fominykh, Ruslan Varvashenya [et al.] | |
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| 330 | |a 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 | ||
| 371 | 0 | |a AM_Agreement | |
| 461 | 1 | |t Molecular Pharmaceutics |c Washington |n ACS Publications | |
| 463 | |t Vol. 23, iss. 4 |v P. 2469–2480 |d 2026 | ||
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a EpCAM | |
| 610 | 1 | |a radionuclide molecular imaging | |
| 610 | 1 | |a DARPin Ec1 | |
| 610 | 1 | |a engineered scaffold proteins | |
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| 701 | 1 | |a Fominykh |b A. S. |g Anastasiya Sergeevna |f 1998- |c chemist |c Engineer of Tomsk Polytechnic University |9 88811 | |
| 701 | 1 | |a Varvashenya |b R. N. |c pharmacist |c engineer at Tomsk Polytechnic University |f 1997- |g Ruslan Nikolaevich |9 88559 | |
| 701 | 1 | |a Yanovich |b G. |c Pharmacist |c engineer of Tomsk Polytechnic University |f 1999- |g Gleb |9 89205 | |
| 701 | 1 | |a Bodenko |b V. V. |c pharmacist |c engineer at Tomsk Polytechnic University |f 1997- |g Vitalina Vasiljevna |9 88553 | |
| 701 | 1 | |a Plotnikov |b E. V. |c chemist |c Associate Professor of Tomsk Polytechnic University, Candidate of Chemical Sciences |f 1983- |g Evgeny Vladimirovich |9 16417 | |
| 701 | 1 | |a Tretyakova (Tretjyakova) |b M. S. |c Medical technology specialist |c Research Engineer of Tomsk Polytechnic University |f 1994- |g Maria Sergeevna |9 22127 | |
| 701 | 1 | |a Eskova |b D. D. |g Darjya Dmitrievna |f 2003- |c biotechnologist |c laboratory assistant of Tomsk Polytechnic University |9 88808 | |
| 701 | 1 | |a Zelchan (Zeltchan) |b R. V. |c specialist in the field of medical technology |c Researcher of the Tomsk Polytechnic University, Candidate of Medical Sciences |f 1984- |g Roman Vladimirovich |9 17728 | |
| 701 | 1 | |a Shulga (Schulga) |b A. A. |c biologist |c Researcher, Tomsk Polytechnic University, Candidate of Biological Sciences |f 1960- |g Aleksey Anatolievich |9 22432 | |
| 701 | 1 | |a Konovalova |b E. V. |c specialist in the field of chemical technology and biotechnology |c engineer at Tomsk Polytechnic University |f 1985- |g Elena Valerjevna |9 88562 | |
| 701 | 1 | |a Ziganshin |b R. |g Rustam | |
| 701 | 1 | |a Orlova |b A. M. |c specialist in the field of medical technology |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D |f 1960- |g Anna Markovna |9 22212 | |
| 701 | 1 | |a Belousov |b M. V. |c chemist |c Professor of Tomsk Polytechnic University, Doctor of Pharmaceutical Sciences |f 1963- |g Mikhail Valerievich |9 21924 | |
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| 701 | 1 | |a Larkina |b M. S. |g Mariya Sergeevna |f 1984- |c pharmacist |c Professor; Senior Researcher of the Tomsk Polytechnic University, Doctor of Pharmaceutical Sciences |9 22417 | |
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