Magnetic resonance imaging visualization of targeted cells by the internalization of supramolecular adducts formed between avidin and biotinylated Gd3+ chelates

J Biol Inorg Chem. 2005 Jan;10(1):78-86. doi: 10.1007/s00775-004-0616-2. Epub 2004 Dec 23.

Abstract

The high binding affinity between avidin and biotin has been exploited to develop a procedure for magnetic resonance imaging (MRI) visualization of target cells. SHIN3 and PANC1 tumor cell lines have been used as target cells because they possess on their membranes galactosyl receptors able to bind avidin molecules. Avidin-Gd chelate adducts have been built by using two Gd complexes containing one (Gd-I) and two (Gd-II) biotin residues, respectively. The relaxivities of such supramolecular adducts are significantly higher than those shown by free Gd-I and Gd-II. There is evidence of the occurrence of multilayered adducts in which the bis-biotinylated Gd(3+) complex acts as a bridge between adjacent avidin molecules. MRI differentiation of labeled versus unlabeled cells has been attained when approximately 6 x 10(8) Gd units were internalized in each cell. Furthermore, there is a marked decrease in the measured intracellular T(1) relaxivity as the number of internalized Gd complexes increases, probably owing to too short relaxation times of endosomic water protons with respect to their diffusion lifetime.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Avidin / chemistry*
  • Avidin / metabolism*
  • Biotin / chemistry
  • Biotin / metabolism*
  • Biotinylation
  • Cell Line, Tumor
  • Chelating Agents / chemistry
  • Chelating Agents / metabolism
  • Chromatography, High Pressure Liquid
  • Gadolinium / chemistry*
  • Gadolinium / metabolism*
  • Humans
  • Ligands
  • Magnetic Resonance Imaging
  • Molecular Structure
  • Titrimetry

Substances

  • Chelating Agents
  • Ligands
  • Avidin
  • Biotin
  • Gadolinium