Investigation using an HER-2/neu transgenic mouse model of a newly developed MR contrast agent with the effect of an antitumor drug

J Magn Reson Imaging. 2009 Oct;30(4):907-10. doi: 10.1002/jmri.21911.

Abstract

Purpose: To assess whether Gd-DTPA-Gel-Cis, a conjugate of gadolinium (Gd), cis diamminedichloroplatinum (Cis), diethylenetriaminepentaacetic acid (DTPA)-dianhydride, and bovine gelatin (Gel) can be used as an intravascular contrast agent at MRI and as an antitumor cell proliferation agent in vitro.

Materials and methods: We injected Gd-DTPA-Gel-Cis (200 mg/mL) into the caudal vein of female HER-2/neu transgenic mice with spontaneous mammary tumors. The tumor signal intensity was measured with a 0.3 Tesla MRI scanner. HER-2/neu-expressing NT cells were treated with Gd-DTPA-Gel-Cis (5 microM cisplatin, 200 mg/mL Gel), Cis alone (5 microM cisplatin), or Gel alone (200 mg/mL gelatin). Differences of P < 0.05 were considered to be statistically significant.

Results: On T1-weighted MRI scans of mice injected with Gd-DTPA-Gel-Cis we observed a 23% increase in signal intensity. The survival rates of cells exposed to Gd-DTPA-Gel-Cis or Cis were 70.9% and 58.3%, respectively, of the survival rates observed after treatment with Gel alone. Gd-DTPA-Gel-Cis showed significant toxicity (P < 0.05).

Conclusion: Gd-DTPA-Gel-Cis shows promise for use as an MRI contrast medium and as an antitumor agent.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cattle
  • Cisplatin / administration & dosage
  • Cisplatin / chemical synthesis
  • Cisplatin / pharmacology*
  • Contrast Media / administration & dosage
  • Contrast Media / chemical synthesis
  • Contrast Media / pharmacology*
  • Cross-Linking Reagents / administration & dosage
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / pharmacology*
  • Disease Models, Animal
  • Female
  • Gadolinium DTPA / administration & dosage
  • Gadolinium DTPA / analogs & derivatives*
  • Gadolinium DTPA / chemical synthesis
  • Gadolinium DTPA / pharmacology*
  • Gelatin / administration & dosage
  • Gelatin / chemical synthesis
  • Gelatin / pharmacology*
  • Genes, erbB-2
  • Magnetic Resonance Imaging / methods*
  • Mammary Neoplasms, Experimental / diagnosis*
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mice
  • Mice, Transgenic

Substances

  • Antineoplastic Agents
  • Contrast Media
  • Cross-Linking Reagents
  • GD-DTPA-Gel-Cis
  • Gelatin
  • Gadolinium DTPA
  • Cisplatin