Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1
| Parent link: | Molecules Vol. 25, iss. 20.— 2020.— [4719, 20 p.] |
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| Autori kompanije: | , |
| Daljnji autori: | , , , , , , , , , |
| Sažetak: | Title screen 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. |
| Jezik: | engleski |
| Izdano: |
2020
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| Teme: | |
| Online pristup: | https://doi.org/10.3390/molecules25204719 |
| Format: | Elektronički Poglavlje knjige |
| KOHA link: | https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=664643 |
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| 200 | 1 | |a Radionuclide Molecular Imaging of EpCAM Expression in Triple-Negative Breast Cancer Using the Scaffold Protein DARPin Ec1 |f A. G. Vorobjeva (Vorobyeva), E. A. Bezverkhniaia, E. V. Konovalova [et al.] | |
| 203 | |a Text |c electronic | ||
| 300 | |a Title screen | ||
| 320 | |a [References: 52 tit.] | ||
| 330 | |a 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. | ||
| 461 | |t Molecules | ||
| 463 | |t Vol. 25, iss. 20 |v [4719, 20 p.] |d 2020 | ||
| 610 | 1 | |a электронный ресурс | |
| 610 | 1 | |a труды учёных ТПУ | |
| 610 | 1 | |a EpCAM | |
| 610 | 1 | |a radionuclide | |
| 610 | 1 | |a molecular imaging | |
| 610 | 1 | |a SPECT | |
| 610 | 1 | |a iodine | |
| 610 | 1 | |a PIB | |
| 610 | 1 | |a breast | |
| 610 | 1 | |a cancer | |
| 610 | 1 | |a радионуклиды | |
| 610 | 1 | |a визуализация | |
| 701 | 1 | |a Vorobjeva (Vorobyeva) |b A. G. |c specialist in the field of medical technology |c Senior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D |f 1990- |g Anzhelika Grigorjevna |3 (RuTPU)RU\TPU\pers\46556 |9 22214 | |
| 701 | 1 | |a Bezverkhniaia |b E. A. |c pharmacist |c Research Engineer Tomsk Polytechnic University |f 1994- |g Ekaterina Aleksandrovna |3 (RuTPU)RU\TPU\pers\46845 |9 22467 | |
| 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 Shulga (Schulga) |b A. A. |c biologist |c Researcher, Tomsk Polytechnic University, Candidate of Biological Sciences |f 1960- |g Aleksey Anatolievich |3 (RuTPU)RU\TPU\pers\46796 |9 22432 | |
| 701 | 1 | |a Garousi |b Ja. |g Javad | |
| 701 | 1 | |a Vorontsova |b O. |g Olga | |
| 701 | 1 | |a Abouzayed |b A. |g Ayman | |
| 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 |3 (RuTPU)RU\TPU\pers\46554 |9 22212 | |
| 701 | 1 | |a Deev |b S. M. |c biologist |c Leading Researcher, Tomsk Polytechnic University, Doctor of Biological Sciences |f 1951- |g Sergey Mikhaylovich |3 (RuTPU)RU\TPU\pers\39299 |9 20959 | |
| 701 | 1 | |a Tolmachev |b V. M. |c specialist in the field of medical technology |c Director of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D |f 1961- |g Vladimir Maksimilianovich |3 (RuTPU)RU\TPU\pers\46552 |9 22210 | |
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