Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Improved contrast of affibody-mediated imaging of HER3 expression in mouse xenograft model through co-injection of a trivalent affibody for in vivo blocking of hepatic uptake
Uppsala Univ, Dept Med Chem, Uppsala, Sweden..
Uppsala Univ, Dept Med Chem, Uppsala, Sweden..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.ORCID iD: 0000-0002-9952-9814
Show others and affiliations
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 6779Article in journal (Refereed) Published
Abstract [en]

Human epidermal growth factor receptor type 3 (HER3) plays a crucial role in the progression of many cancer types. In vivo radionuclide imaging could be a reliable method for repetitive detection of HER3-expression in tumors. The main challenge of HER3-imaging is the low expression in tumors together with endogenous receptor expression in normal tissues, particularly the liver. A HER3-targeting affibody molecule labeled with radiocobalt via a NOTA chelator [Co-57]Co-NOTA-Z(08699) has demonstrated the most favorable biodistribution profile with the lowest unspecific hepatic uptake and high activity uptake in tumors. We hypothesized that specific uptake of labeled affibody monomer might be selectively blocked in the liver but not in tumors by a co-injection of non-labeled corresponding trivalent affibody (Z(08699))(3). Biodistribution of [Co-57]Co-NOTA-Z(08699) and [In-111]ln-DOTA-(Z(08699))(3) was studied in BxPC-3 xenografted mice. [Co-57]Co-NOTA-Z(08699) was co-injected with unlabeled trivalent affibody DOTA-(Z(08699))(3) at different monomer:trimer molar ratios. HER3-expression in xenografts was imaged using [Co-57]Co-NOTA-Z(08699) and [Co-57]Co-NOTA-Z(08699): DOTA-(Z(08699))(3). Hepatic activity uptake of [Co-57] Co-NOTA-Z(08699): DOTA-(Z(08699))(3) decreased with increasing monomer:trimer molar ratio. The tumor activity uptake and tumor-to-liver ratios were the highest for the 1:3 ratio. SPECT/CT images confirmed the biodistribution data. Imaging of HER3 expression can be improved by co-injection of a radiolabeled monomeric affi body-based imaging probe together with a trivalent affibody.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 9, article id 6779
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:kth:diva-270659DOI: 10.1038/s41598-019-43145-2ISI: 000466358700048PubMedID: 31043683Scopus ID: 2-s2.0-85065179852OAI: oai:DiVA.org:kth-270659DiVA, id: diva2:1416876
Note

QC 20200325

Available from: 2020-03-25 Created: 2020-03-25 Last updated: 2020-03-25Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Andersson, Ken G.Leitao, Charles DahlssonStåhl, StefanLöfblom, John

Search in DiVA

By author/editor
Andersson, Ken G.Leitao, Charles DahlssonMitran, BogdanVorobyeva, AnzhelikaStåhl, StefanLöfblom, JohnTolmachev, VladimirOrlova, Anna
By organisation
Protein ScienceAlbanova VinnExcellence Center for Protein Technology, ProNovaProtein Engineering
In the same journal
Scientific Reports
Radiology, Nuclear Medicine and Medical Imaging

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 18 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf