SwePub
Sök i LIBRIS databas

  Utökad sökning

id:"swepub:oai:DiVA.org:kth-249778"
 

Sökning: id:"swepub:oai:DiVA.org:kth-249778" > Site-specific conju...

  • Westerlund, KristinaKTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, S-10691 Stockholm, Sweden (författare)

Site-specific conjugation of recognition tags to trastuzumab for peptide nucleic acid-mediated radionuclide HER2 pretargeting

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • ELSEVIER SCI LTD,2019
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:kth-249778
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-249778URI
  • https://doi.org/10.1016/j.biomaterials.2019.02.012DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-382376URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • QC 20190429
  • Pretargeting is a promising strategy to reach high imaging contrast in a shorter time than by targeting with directly radiolabeled monoclonal antibodies (mAbs). One of problems in pretargeting is a site-specific, reproducible and uniform conjugation of recognition tags to mAbs. To solve this issue we propose a photoconjugation to covalently couple a recognition tag to a mAb via a photoactivatable Z domain. The Z-domain, a 58-amino acid protein derived from the IgG-binding B-domain of Staphylococcus aureus protein A, has a well-characterized binding site in the Fc portion of IgG. We tested the feasibility of this approach using pretargeting based on hybridization between peptide nucleic acids (PNAs). We have used photoconjugation to couple trastuzumab with the PNA-based hybridization probe, HP1. A complementary [Co-57]Co-labeled PNA hybridization probe ([Co-57]Co-HP2) was used as the secondary targeting probe. In vitro studies demonstrated that trastuzumab-ZHP1 bound specifically to human epidermal growth factor receptor 2 (HER2)-expressing cells with nanomolar affinity. The binding of the secondary [Co-57]Co-HP2 probe to trastuzumab-PNA-pretreated cells was in the picomolar affinity range. A two-fold increase in SKOV-3 tumor targeting was achieved when [Co-57]Co-HP2 (0.7 nmol) was injected 48 h after injection of trastuzumab-ZHP1 (0.5 nmol) compared with trastuzumab-ZHP1 alone (0.8 +/- 0.2 vs. 0.33 +/- 0.06 %ID/g). Tumor accumulation of [Co-57]Co-HP2 was significantly reduced by pre-saturation with trastuzumab or when no trastuzumab-ZHP1 was preinjected. A tumor-to-blood uptake ratio of 1.5 +/- 0.3 was achieved resulting in a clear visualization of HER2-expressing xenografts as confirmed by SPECT imaging. In conclusion, the feasibility of stable site-specific coupling of a PNA-based recognition tag to trastuzumab and successful pretargeting has been demonstrated. This approach can hopefully be used for a broad range of mAbs and recognition tags.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Vorobyeva, AnzhelikaUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)anzvo555 (författare)
  • Mitran, BogdanUppsala universitet,Theranostics(Swepub:uu)mitbo652 (författare)
  • Orlova, Anna,1960-Uppsala universitet,Theranostics(Swepub:uu)annaorlo (författare)
  • Tolmachev, VladimirUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)vladtolm (författare)
  • Eriksson Karlström, AmelieKTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, S-10691 Stockholm, Sweden(Swepub:kth)u10x6l4n (författare)
  • Altai, MohamedUppsala universitet,Medicinsk strålningsvetenskap(Swepub:uu)mohal988 (författare)
  • KTHProteinvetenskap (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Biomaterials: ELSEVIER SCI LTD203, s. 73-850142-96121878-5905

Internetlänk

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy