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Effect of a radiola...
Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec1
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- Deyev, Sergey M. (author)
- Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.;Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.;Sechenov Univ, Ctr Biomed Engn, Moscow, Russia.
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- Vorobyeva, Anzhelika (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia
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- Schulga, Alexey (author)
- Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.;Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.
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- Abouzayed, Ayman (author)
- Uppsala universitet,Theranostics
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- Gunther, Tyran (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Garousi, Javad (author)
- Uppsala universitet,Medicinsk strålningsvetenskap
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- Konovalova, Elena (author)
- Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.
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- Ding, Haozhong (author)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden
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- Gräslund, Torbjörn (author)
- KTH,Albanova VinnExcellence Center for Protein Technology, ProNova,Proteinvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Stockholm, Sweden
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- Orlova, Anna, 1960- (author)
- Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab,Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Medicinsk strålningsvetenskap,Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia
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Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia;Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.;Sechenov Univ, Ctr Biomed Engn, Moscow, Russia. Medicinsk strålningsvetenskap (creator_code:org_t)
- ELSEVIER, 2020
- 2020
- English.
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In: International Journal of Biological Macromolecules. - : ELSEVIER. - 0141-8130 .- 1879-0003. ; 145, s. 216-225
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Abstract
Subject headings
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- Radionuclide-based imaging of molecular therapeutic targets might facilitate stratifying patients for specific biotherapeutics. New type of imaging probes, based on designed ankyrin repeat proteins (DARPins), have demonstrated excellent contrast of imaging of human epidermal growth factor type 2 (HER2) expression in preclinical models. We hypothesized that labeling approaches, which result in lipophilic radiometabolites (non-residualizing labels), would provide the best imaging contrast for DARPins that internalize slowly after binding to cancer cells. The hypothesis was tested using DARPin Ec1 that binds to epithelial cell adhesion molecule (EpCAM). EpCAM is a promising therapeutic target. Ec1 was labeled with I-125 using two methods to obtain the non-residualizing labels, while residualizing labels were obtained by labeling it with Tc-99m. All labeled Ec1 variants preserved target specificity and picomolar binding affinity to EpCAM-expressing pancreatic adenocarcinoma BxPC-3 cells. In murine models, all the variants provided similar tumor uptake. However, I-125-PIB-H-6-Ec1 had noticeably lower retention in normal tissues, which provided appreciably higher tumor-to-organ ratios. Furthermore, I-125-PIB-H-6-Ec1 demonstrated the highest imaging contrast in preclinical models than any other EpCAM-imaging agent tested so far. In conclusion, DARPin Ec1 in combination with a non-residualizing label is a promising probe for imaging EpCAM expression a few hours after injection.
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)
Keyword
- Designed ankyrin repeat protein
- EpCAM
- Labeling
- Structure-property relationship
- Biodistribution
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Deyev, Sergey M.
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Vorobyeva, Anzhe ...
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Schulga, Alexey
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Abouzayed, Ayman
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Gunther, Tyran
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Garousi, Javad
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Konovalova, Elen ...
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Ding, Haozhong
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Gräslund, Torbjö ...
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Orlova, Anna, 19 ...
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Tolmachev, Vladi ...
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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 ...
- Articles in the publication
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International Jo ...
- By the university
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Royal Institute of Technology
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Uppsala University