Effects of affinity on binding of HER2-targeting Affibody molecules: Model experiments in breast cancer spheroids

Research output: Contribution to journalArticle

Abstract

Binding of a targeting agent in tumor tissue is influenced by many factors such as molecular weight, charge and affinity of the targeting agent and vascularization of the tumor. In this study, we analyzed tumor cell binding of three HER2-specific and radiolabeled Affibody molecules with different affinities. The Affibody molecules had affinities in the range of 0.12-3.8 nM. Cellular binding was analyzed, after 2 h of incubation, in tumor spheroids composed of BT474 breast cancer cells, which highly express HER2. Binding was, due to the binding-site barrier,limited to the outer 15 +/- 5 mu m rim of the spheroids, independent of affinity when the concentration of the substances was low. When the concentration was high, the binding site barrier was overcome and the binding occurred approximately 35 +/- 5 mu m into the spheroids for the two high affinity substances and 50 +/- 5 mu m for the low affinity substance. The lower affinity might allow for penetration into deeper regions due to less firm binding. We conclude that there is a binding site barrier within tumor spheroids which can be overcome by increased concentration of substance and modified by affinity.

Details

Authors
  • O. F. Qvarnstrom
  • M. Simonsson
  • J. Carlsson
  • Thuy Tran
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Affibody, affinity, binding, breast cancer cells, BT474, cell, spheroids, compound development, HER2, penetration, radionuclides, binding-site barrier
Original languageEnglish
Pages (from-to)353-359
JournalInternational Journal of Oncology
Volume39
Issue number2
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes