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Comparative Preclin...
Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer
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- Larkina, Mariia (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia.
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- Plotnikov, Evgenii (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Bezverkhniaia, Ekaterina (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia.
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- Shabanova, Yulia (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Tretyakova, Maria (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Yuldasheva, Feruza (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Zelchan, Roman (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Russian Acad Sci, Tomsk Natl Res Med Ctr, Canc Res Inst, Dept Nucl Med, Tomsk 634009, Russia.
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- Schulga, Alexey (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.
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- Konovalova, Elena (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Cancerprecisionsmedicin
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- Garousi, Javad (author)
- Uppsala universitet,KTH,Proteinvetenskap,Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.,Cancerprecisionsmedicin,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, S-11417 Stockholm, Sweden.
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- Gräslund, Torbjörn, 1970- (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, S-11417 Stockholm, Sweden.
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- Belousov, Mikhail (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia.
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Cancerprecisionsmedicin,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.
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- Deyev, Sergey (author)
- Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia.
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Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia. Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia. (creator_code:org_t)
- 2022-11-03
- 2022
- English.
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:21, s. 13443-
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Abstract
Subject headings
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- Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [Tc-99m]Tc-(HE)(3)-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)(3)), provided clear imaging of HER2 expressing breast cancer 2-4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G(3)C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)(3)-linker (designated as G3-(G(3)S)(3)C) would further improve the contrast of imaging using Tc-99m-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9-5 nM. Biodistribution of [Tc-99m]Tc-G3-G(3)C, [Tc-99m]Tc-G3-(G(3)S)(3)C, and [Tc-99m]Tc-G3-E3C in mice was compared with the biodistribution of [Tc-99m]Tc-(HE)(3)-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [Tc-99m]Tc-(HE)(3)-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- radionuclide
- HER2
- DARPin
- SPECT
- Tc-99m
- imaging
- cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Larkina, Mariia
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Plotnikov, Evgen ...
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Bezverkhniaia, E ...
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Shabanova, Yulia
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Tretyakova, Mari ...
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Yuldasheva, Feru ...
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Zelchan, Roman
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Schulga, Alexey
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Konovalova, Elen ...
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Vorobyeva, Anzhe ...
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Garousi, Javad
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Gräslund, Torbjö ...
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Belousov, Mikhai ...
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Tolmachev, Vladi ...
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Deyev, Sergey
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Radiology Nuclea ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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Royal Institute of Technology
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Uppsala University