Alginate-coated magnetic nanoparticles for noninvasive MRI of extracellular calcium

Amnon Bar-Shir, Liat Avram, Shani Yariv-Shoushan, Debbie Anaby, Smadar Cohen, Niva Segev-Amzaleg, Dan Frenkel, Ofer Sadan, Daniel Offen, Yoram Cohen

Research output: Contribution to journalArticlepeer-review


Nanoparticles (NPs) have great potential to increase the diagnostic capacity of many imaging modalities. MRI is currently regarded as the method of choice for the imaging of deep tissues, and metal ions, such as calcium ions (Ca2+), are essential ingredients for life. Despite the tremendous importance of Ca2+ for the well-being of living systems, the noninvasive determination of the changes in Ca2+ levels in general, and extracellular Ca2+ levels in particular, in deep tissues remains a challenge. Here, we describe the preparation and contrast mechanism of a flexible easy to prepare and selective superparamagnetic iron oxide (SPIO) NPs for the noninvasive determination of changes in extracellular Ca2+ levels using conventional MRI. We show that SPIO NPs coated with monodisperse and purified alginate, having a specific molecular weight, provide a tool to selectively determine Ca2+ concentrations in the range of 250μm to 2.5mm, even in the presence of competitive ions. The alginate-coated magnetic NPs (MNPs) aggregate in the presence of Ca2+, which, in turn, affects the T2 relaxation of the water protons in their vicinity. The new alginate-coated SPIO NP formulations, which have no effect on cell viability for 24h, allow the detection of Ca2+ levels secreted from ischemic cell cultures and the qualitative examination of the change in extracellular Ca2+ levels in vivo. These results demonstrate that alginate-coated MNPs can be used, at least qualitatively, as a platform for the noninvasive MRI determination of extracellular Ca2+ levels in myriad in vitro and in vivo biomedical applications.

Original languageEnglish (US)
Pages (from-to)774-783
Number of pages10
JournalNMR in biomedicine
Issue number7
StatePublished - Jul 2014
Externally publishedYes


  • Alginates
  • Calcium sensing
  • Contrast agents
  • MRI
  • Magnetic nanoparticles
  • Molecular MRI

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy


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