Optimization of HER3 expression imaging using affibody molecules: Influence of chelator for labeling with indium-111. Academic Article uri icon

Overview

abstract

  • Radionuclide molecular imaging of human epidermal growth factor receptor 3 (HER3) expression using affibody molecules could be used for patient stratification for HER3-targeted cancer therapeutics. We hypothesized that the properties of HER3-targeting affibody molecules might be improved through modification of the radiometal-chelator complex. Macrocyclic chelators NOTA (1,4,7-triazacyclononane-N,N',N''-triacetic acid), NODAGA (1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), and DOTAGA (1,4,7,10-tetraazacyclododececane,1-(glutaric acid)-4,7,10-triacetic acid) were conjugated to the C-terminus of anti-HER3 affibody molecule Z08698 and conjugates were labeled with indium-111. All conjugates bound specifically and with picomolar affinity to HER3 in vitro. In mice bearing HER3-expressing xenografts, no significant difference in tumor uptake between the conjugates was observed. Presence of the negatively charged 111In-DOTAGA-complex resulted in the lowest hepatic uptake and the highest tumor-to-liver ratio. In conclusion, the choice of chelator influences the biodistribution of indium-111 labeled anti-HER3 affibody molecules. Hepatic uptake of anti-HER3 affibody molecules could be reduced by the increase of negative charge of the radiometal-chelator complex on the C-terminus without significantly influencing the tumor uptake.

authors

  • Rinne, Sara
  • Leitao, Charles Dahlsson
  • Mitran, Bogdan
  • Bass, Tarek Z
  • Andersson, Ken G
  • Tolmachev, Vladimir
  • Ståhl, Stefan
  • Löfblom, John
  • Orlova, Anna

publication date

  • January 24, 2019

Research

keywords

  • Chelating Agents
  • Gene Expression Regulation
  • Indium Radioisotopes
  • Receptor, ErbB-3
  • Recombinant Proteins
  • Single Photon Emission Computed Tomography Computed Tomography

Identity

PubMed Central ID

  • PMC6345776

Scopus Document Identifier

  • 85060519832

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-05700-7

PubMed ID

  • 30679757

Additional Document Info

volume

  • 9

issue

  • 1