In vivo imaging of human breast cancer mouse model with high level expression of calcium sensing receptor at 3T
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).
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 MnCl2. To block the CaSR-activated Ca2+ channels, verapamil was injected at the tumour site 5 min before Mn2+ administration. CaSR expression in vivo was studied by immunohistochemistry.
Contrast enhancement was observed at the tumour periphery 10 min after Mn2+ 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.
Manganese enhanced magnetic resonance imaging can visualise CaSR-expressing breast cancer cells in vivo, opening up possibilities for a new MR contrast agent.
• 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.
KeywordsMagnetic Resonance Imaging Manganese chloride Breast cancer Calcium receptor In vivo small animal MRI
The authors thank Dr. Silvano Ferrini for his helpful discussions and revision of the manuscript.
This study was supported by the Italian Ministry of Health ‘Progetto oncologico di Medicina Molecolare: i tumori femminili’.
- 11.Prentince A, Jarjou LMA, Cole TJ et al (1995) Calcium requirements of lactating Gambian mothers, effects of a calcium supplement on breast-milk calcium concentration, maternal bone mineral content and urinary calcium excretion. Am J Clin Nutr 62:58–67Google Scholar
- 21.Nemeth EF, Fox J, Delmar EG et al (1998) Stimulation of parathyroid hormone secretion by a small molecule antagonist of the calcium receptor (Abstract). J Bone Miner Res 23:S156Google Scholar
- 33.Lin Y (1997) MRI of the rat and mouse brain after systemic administration of MnCl2. Thesis, Carnegie Mellon University, Pittsburgh, PAGoogle Scholar
- 37.van Zijl PC, Place DA, Cohen JS et al (1990) Metalloporphyrin magnetic resonance contrast agents. Feasibility of tumour-specific magnetic resonance imaging. Acta Radiol 374:75–79Google Scholar
- 46.Aydar E, Yeo S, Djamgoz M, Palmer C (2009) Abnormal expression, localization and interaction of canonical transient receptor potential ion channels in human breast cancer cell lines and tissues: a potential target for breast cancer diagnosis and therapy. Cancer Cell Int 18:9–23Google Scholar