Gadolinium complex of DO3A-benzothiazole aniline (BTA) conjugate as a theranostic agent

J Med Chem. 2013 Oct 24;56(20):8104-11. doi: 10.1021/jm401206t. Epub 2013 Oct 10.

Abstract

A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of structurally analogous Gd-DOTA. The same complex is not only tumor-specific but also intracellular, enhancing MR images of cytosols and nuclei of tumor cells such as MCF-7, MDA-MB-231, and SK-HEP-1. Both DO3A-BTA and Gd(DO3A-BTA) reveal antiproliferative activities as demonstrated by GI50 and TGI values obtainable from the cell counting kit-8 (CCK-8) assays performed on these cell lines. Ex vivo and in vivo monitoring of tumor sizes provide parallel and supportive observations for such antiproliferative activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzothiazoles / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Contrast Media / chemistry
  • Female
  • Gadolinium / chemistry*
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Humans
  • MCF-7 Cells
  • Magnetic Resonance Imaging / methods
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Structure
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / pharmacology
  • Sensitivity and Specificity
  • Xenograft Model Antitumor Assays

Substances

  • 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  • Benzothiazoles
  • Contrast Media
  • Heterocyclic Compounds, 1-Ring
  • Organometallic Compounds
  • Gadolinium
  • benzothiazole