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  • Deyev, Sergey M.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.;Natl Res Nucl Univ MEPhI, Inst Engn Phys Biomed PhysBio, Bionanophoton Lab, Moscow 115409, Russia. (author)

Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-07-17
  • MDPI AG,2021
  • printrdacarrier

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  • LIBRIS-ID:oai:DiVA.org:kth-299292
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-299292URI
  • https://doi.org/10.3390/cancers13143589DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-451784URI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • QC 20210823
  • Simple Summary Metastasis-targeting therapy might improve outcomes in oligometastatic prostate cancer. Epithelial cell adhesion molecule (EpCAM) is overexpressed in 40-60% of prostate cancer cases and might be used as a target for specific delivery of toxins and drugs. Radionuclide molecular imaging could enable non-invasive detection of EpCAM and stratification of patients for targeted therapy. Designed ankyrin repeat proteins (DARPins) are scaffold proteins, which can be selected for specific binding to different targets. The DARPin Ec1 binds strongly to EpCAM. To determine an optimal design of Ec1-based probes, we labeled Ec1 at two different positions with four different nuclides (Ga-68, In-111, Co-57 and I-125) and investigated the impact on Ec1 biodistribution. We found that the C-terminus is the best position for labeling and that In-111 and I-125 provide the best imaging contrast. This study might be helpful for scientists developing imaging probes based on scaffold proteins. The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40-60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy. The study aimed to investigate the influence of radiolabel position (N- or C-terminal) and composition on the targeting and imaging properties of Ec1. Two variants, having an N- or C-terminal cysteine, were produced, site-specifically conjugated to a DOTA chelator and labeled with cobalt-57, gallium-68 or indium-111. Site-specific radioiodination was performed using ((4-hydroxyphenyl)-ethyl)maleimide (HPEM). Biodistribution of eight radiolabeled Ec1-probes was measured in nude mice bearing PCa DU145 xenografts. In all cases, positioning of a label at the C-terminus provided the best tumor-to-organ ratios. The non-residualizing [I-125]I-HPEM label provided the highest tumor-to-muscle and tumor-to-bone ratios and is more suitable for EpCAM imaging in early-stage PCa. Among the radiometals, indium-111 provided the highest tumor-to-blood, tumor-to-lung and tumor-to-liver ratios and could be used at late-stage PCa. In conclusion, label position and composition are important for the DARPin Ec1.

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  • Xu, TianqiUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)tiaxu272 (author)
  • Liu, YongshengUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)yonli549 (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, ElenaRussian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Mol Immunol Lab, Moscow 117997, Russia. (author)
  • Garousi, JavadUppsala universitet,KTH,Proteinvetenskap,Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.,Medicinsk strålningsvetenskap,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-11417 Stockholm, Sweden.(Swepub:uu)javga723 (author)
  • Rinne, Sara S.Uppsala universitet,Theranostics(Swepub:uu)sarri895 (author)
  • Larkina, MariaTomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.;Siberian State Med Univ SSMU, Dept Pharmaceut Anal, 2 Moscow Trakt, Tomsk 634050, Russia. (author)
  • Ding, HaozhongKTH,Proteinvetenskap,Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-11417 Stockholm, Sweden.,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-11417 Stockholm, Sweden.(Swepub:kth)u18o3ynm (author)
  • Gräslund, TorbjörnKTH,Albanova VinnExcellence Center for Protein Technology, ProNova,Proteinvetenskap,Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-11417 Stockholm, Sweden.,KTH Royal Inst Technol, Dept Prot Sci, Sch Engn Sci Chem Biotechnol & Hlth, S-11417 Stockholm, Sweden.(Swepub:kth)u1dl39rj (author)
  • Orlova, Anna,1960-Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.(Swepub:uu)annaorlo (author)
  • Tolmachev, VladimirUppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.(Swepub:uu)vladtolm (author)
  • Vorobyeva, AnzhelikaUppsala universitet,Medicinsk strålningsvetenskap,Tomsk Polytech Univ, Res Ctr Oncotheranost, Res Sch Chem & Appl Biomed Sci, Tomsk 634050, Russia.(Swepub:uu)anzvo555 (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.;Natl Res Nucl Univ MEPhI, Inst Engn Phys Biomed PhysBio, Bionanophoton Lab, Moscow 115409, Russia.Medicinsk strålningsvetenskap (creator_code:org_t)

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