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  • Larkina, MariiaTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia. (author)

Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with 99mTc for Radionuclide Imaging of HER2 Expression in Cancer

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-11-03
  • MDPI AG,2022
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:kth-322217
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-322217URI
  • https://doi.org/10.3390/ijms232113443DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-489722URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20221205
  • 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.

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  • Plotnikov, EvgeniiTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia. (author)
  • Bezverkhniaia, EkaterinaTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia. (author)
  • Shabanova, YuliaTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia. (author)
  • Tretyakova, MariaTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia. (author)
  • Yuldasheva, FeruzaTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia. (author)
  • Zelchan, RomanTomsk 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. (author)
  • Schulga, AlexeyTomsk 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. (author)
  • Konovalova, ElenaTomsk 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. (author)
  • Vorobyeva, AnzhelikaUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)anzvo555 (author)
  • Garousi, JavadUppsala 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.(Swepub:uu)javga723 (author)
  • Gräslund, Torbjörn,1970-KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, S-11417 Stockholm, Sweden.(Swepub:kth)u1dl39rj (author)
  • Belousov, MikhailTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ, Dept Pharmaceut Anal, Tomsk 634050, Russia. (author)
  • Tolmachev, VladimirUppsala universitet,Cancerprecisionsmedicin,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.(Swepub:uu)vladtolm (author)
  • Deyev, SergeyTomsk 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. (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.Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia. (creator_code:org_t)

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  • In:International Journal of Molecular Sciences: MDPI AG23:21, s. 13443-1661-65961422-0067

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