MRI is a very good way of observing anatomical structures in soft biological tissue without the need for ionizing radiation or dangerous radionuclides. MR images are obtained by exciting the protons found in water and fat inside the body with a magnetic field and then measuring the rate that these protons relax back to their original state. These proton relaxation times are different for different tissues, which results in the MR contrast in the final image.

The proton relaxation itself can be described by a parameter called relaxivity (r1), or contrast enhancement efficiency, and defines how bright the contrast will appear in an MR image.

Researchers have also developed several nanoparticle MRI contrast agents that respond to factors like pH. This is important for imaging tumours because the pH inside a tumour is generally lower (more acidic), at around 6.6, compared to healthy tissue, which has a pH of around 7.4.

Imaging hypoxic regions in tumours

A team led by Kazunori Kataoka at the University of Tokyo and iCONM in Kawasaki has now developed a new MRI contrast agent made from Mn2+ ions confined inside pH-sensitive CaP nanoparticles with a poly(ethylene glycol) shell. At low pH, the CaP disintegrates and releases Mn2+ ions. After the Mn2+ ions have bound to proteins, their r1 increases and thus greatly enhances the contrast in the MR images obtained. Indeed, in experiments on tumour-bearing mice, the researchers found that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic (or low oxygen) regions within the tumour mass and so unearth millimetre-sized metastatic tumours that would have otherwise remained invisible.

“Our nanoparticle contrast agents could be used to detect tumour malignancy thanks to the fact that they can image hypoxic regions in them, as well as micrometastasis,” team member Peng Mi tells nanotechweb.org. “Being able to successfully detect hypoxia is very important for proper treatment, since it is related to therapeutic resistance, a major reason for why many anti-cancer drugs fail. Tumour metastasis, for its part, causes 90% of all cancer related deaths.”

The researchers, reporting their work in Nature Nanotechnology doi:10.1038/nnano.2016.72, say they would now like to test out their contrast agents in pre-clinical and clinical trials.