Synthesis and relaxivity studies of a DOTA-based nanomolecular chelator assembly supported by an icosahedral closo-B₁₂²⁻ core for MRI: a click chemistry approach

Molecules. 2013 Jul 29;18(8):9034-48. doi: 10.3390/molecules18089034.

Abstract

An icosahedral closo-B₁₂²⁻ scaffold based nano-sized assembly capable of carrying a high payload of Gd³⁺-chelates in a sterically crowded configuration is developed by employing the azide-alkyne click reaction. The twelve copies of DO3A-t-Bu-ester ligands were covalently attached to an icosahedral closo-B₁₂²⁻ core via suitable linkers through click reaction. This nanomolecular structure supporting a high payload of Gd³⁺-chelate is a new member of the closomer MRI contrast agents that we are currently developing in our laboratory. The per Gd ion relaxivity (r₁) of the newly synthesized MRI contrast agent was obtained in PBS, 2% tween/PBS and bovine calf serum using a 7 Tesla micro MRI instrument and was found to be slightly higher (r₁ = 4.7 in PBS at 25 °C) compared to the clinically used MRI contrast agents Omniscan (r₁ = 4.2 in PBS at 25 °C) and ProHance (r₁ = 3.1 in PBS at 25 °C).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes / chemistry
  • Azides / chemistry
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Click Chemistry*
  • Contrast Media / chemical synthesis*
  • Contrast Media / chemistry
  • Gadolinium / chemistry
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Ligands
  • Magnetic Resonance Imaging*
  • Organometallic Compounds / chemistry

Substances

  • 1,4,7-tris(tert-butylacetate)-1,4,7,10-tetraazacyclododecane ester
  • Alkynes
  • Azides
  • Chelating Agents
  • Contrast Media
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Ligands
  • Organometallic Compounds
  • gadoteridol
  • Gadolinium