In vivo imaging of human breast cancer mouse model with high level expression of calcium sensing receptor at 3T

Eur Radiol. 2012 Mar;22(3):551-8. doi: 10.1007/s00330-011-2285-1. Epub 2011 Sep 24.

Abstract

Objectives: To demonstrate that manganese can visualise calcium sensing receptor (CaSR)-expressing cells in a human breast cancer murine model, as assessed by clinical 3T magnetic resonance (MR).

Methods: Human MDA-MB-231-Luc or MCF7-Luc breast cancer cells were orthotopically grown in NOD/SCID mice to a minimum mass of 5 mm. Mice were evaluated on T1-weighted sequences before and after intravenous injection of MnCl(2). To block the CaSR-activated Ca(2+) channels, verapamil was injected at the tumour site 5 min before Mn(2+) administration. CaSR expression in vivo was studied by immunohistochemistry.

Results: Contrast enhancement was observed at the tumour periphery 10 min after Mn(2+) administration, and further increased up to 40 min. In verapamil-treated mice, no contrast enhancement was observed. CaSR was strongly expressed at the tumour periphery.

Conclusion: Manganese enhanced magnetic resonance imaging can visualise CaSR-expressing breast cancer cells in vivo, opening up possibilities for a new MR contrast agent.

Key points: • Manganese contrast agents helped demonstrate breast cancer cells in an animal model. • Enhancement was most marked in cells with high calcium sensing receptor expression. • Manganese uptake was related to the distribution of CaSR within the tumour. • Manganese MRI may become useful to investigate human breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Chlorides / administration & dosage
  • Chlorides / pharmacokinetics*
  • Contrast Media / administration & dosage
  • Contrast Media / pharmacokinetics*
  • Disease Models, Animal
  • Female
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging / methods*
  • Manganese Compounds / administration & dosage
  • Manganese Compounds / pharmacokinetics*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Receptors, Calcium-Sensing / metabolism*
  • Verapamil / administration & dosage
  • Verapamil / pharmacokinetics*

Substances

  • Chlorides
  • Contrast Media
  • Manganese Compounds
  • Receptors, Calcium-Sensing
  • Verapamil
  • manganese chloride