SwePub
Sök i LIBRIS databas

  Extended search

WFRF:(Sandström Lars)
 

Search: WFRF:(Sandström Lars) > Targeting of HER2-E...

  • Ahlgren, SaraUppsala universitet,Institutionen för medicinska vetenskaper (author)

Targeting of HER2-Expressing Tumors Using 111In-ABY-025, a Second-Generation Affibody Molecule with a Fundamentally Reengineered Scaffold

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • 2010-06-16
  • Society of Nuclear Medicine,2010
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-122176
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-122176URI
  • https://doi.org/10.2967/jnumed.109.073346DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

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

Notes

  • Overexpression of HER2 in breast carcinomas predicts response to trastuzumab therapy. Affibody molecules based on a non-immunoglobulin scaffold have demon-strated high potential for in vivo molecular imaging of HER2-expressing tumors. Re-engineering of the molecular scaffold has led to a second generation of optimized Affibody molecules, having a surface distinctly different from the parental protein domain from staphylococcal protein A. The new tracer showed further increased melting point, stability and overall hydrophilicity compared to the parental molecule, and was shown to be more amenable for chemical peptide synthesis. The goal of this study was to assess potential effects of this extensive re-engineering on HER2 targeting, using ABY-025, a DOTA conjugated variant of the novel tracer. Methods: 111In-ABY-025 was compared with previously evaluated parent HER2-binding Affibody tracers in vitro and in vivo. The in vivo behavior was further evaluated in mice bearing SKOV-3 xenografts, in rats and in cynomolgus macaques. Results: 111In-ABY-025 bound specifically to HER2 in vitro and in vivo. Direct comparison with the previous generation of HER2-binding tracers showed that ABY-025 retained excellent targeting properties. Rapid blood clearance was shown in mice, rats and macaques. A highly specific tumor uptake of 16.7 ± 2.5 %IA/g was seen at 4 h after injection. The tumor-to-blood ratio was 6.3 at 0.5 h, 88 at 4 h, and increased up to 3 days after injection. Gamma camera imaging of tumors was already possible 0.5 h after injection. Furthermore, repeated i.v. administration of ABY-025 did not induce antibody formation in rats. Conclusions: The biodistribution of 111In-ABY-025 was in remarkably good agreement with the parent tracers, despite profound re-engineering of the non-binding surface. The molecule displayed rapid blood clearance in all species investigated and excellent targeting capacity in tumor bearing mice, leading to high tumor-to-organ-ratios and high contrast imaging shortly after injection.

Subject headings and genre

  • MEDICINE
  • MEDICIN

Added entries (persons, corporate bodies, meetings, titles ...)

  • Orlova, AnnaUppsala universitet,Institutionen för radiologi, onkologi och strålningsvetenskap,BMS(Swepub:uu)annaorlo (author)
  • Wållberg, HelenaAffibody AB, Stockholm, Sweden (author)
  • Hansson, MonikaAffibody AB, Stockholm, Sweden (author)
  • Sandström, MattiasUppsala universitet,Enheten för onkologi(Swepub:uu)masan637 (author)
  • Lewsley, RichardDepartment of Metabolism, Covance Laboratories Ltd, Harrogate, UK (author)
  • Wennborg, AndersAffibody AB, Stockholm, Sweden (author)
  • Abrahmsén, LarsAffibody AB, Stockholm, Sweden (author)
  • Tolmachev, VladimirUppsala universitet,Institutionen för medicinska vetenskaper,Institutionen för radiologi, onkologi och strålningsvetenskap,BMS(Swepub:uu)vladtolm (author)
  • Feldwisch, JoachimUppsala universitet,Institutionen för radiologi, onkologi och strålningsvetenskap,BMS (author)
  • Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

Related titles

  • In:Journal of Nuclear Medicine: Society of Nuclear Medicine51:7, s. 1131-11380161-55051535-56672159-662X

Internet link

Find in a library

To the university's database

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 Close

Copy and save the link in order to return to this view