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

Qvarnstrom, O. F.; Simonsson, M.; Carlsson, J. and Tran, Thuy LU (2011) In International Journal of Oncology 39(2). p.353-359
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Affibody, affinity, binding, breast cancer cells, BT474, cell, spheroids, compound development, HER2, penetration, radionuclides, binding-site barrier
in
International Journal of Oncology
volume
39
issue
2
pages
353 - 359
publisher
D.A. Spandidos
external identifiers
  • wos:000292623700007
  • scopus:79960001863
ISSN
1019-6439
DOI
10.3892/ijo.2011.1045
language
English
LU publication?
yes
id
b38775c6-4a6d-4b25-b8aa-28d671d3c473 (old id 2094143)
date added to LUP
2011-09-02 08:35:11
date last changed
2017-01-01 06:14:20
@article{b38775c6-4a6d-4b25-b8aa-28d671d3c473,
  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.},
  author       = {Qvarnstrom, O. F. and Simonsson, M. and Carlsson, J. and Tran, Thuy},
  issn         = {1019-6439},
  keyword      = {Affibody,affinity,binding,breast cancer cells,BT474,cell,spheroids,compound development,HER2,penetration,radionuclides,binding-site barrier},
  language     = {eng},
  number       = {2},
  pages        = {353--359},
  publisher    = {D.A. Spandidos},
  series       = {International Journal of Oncology},
  title        = {Effects of affinity on binding of HER2-targeting Affibody molecules: Model experiments in breast cancer spheroids},
  url          = {http://dx.doi.org/10.3892/ijo.2011.1045},
  volume       = {39},
  year         = {2011},
}