22 August 2005: Targeted nanoprobes for cancer detection and prognosis

Magnetic nanocrystals have been bound to cancer-targeting antibodies to create a highly sensitive probe for the detection of cancer in vivo.

Magnetic resonance imaging (MRI) can distinguish between different types of living tissue by highlighting the differences in water content and blood flow. In the case of cancer, tumours tend to have higher blood flow than the surrounding, benign tissue, enabling them to be detected.

One major drawback of MRI is its low signal sensitivity, and various contrast agents and probes have been employed to improve image quality. Now, Korean researchers have devised a cancer probe based on magnetic nanocrystals bound to a cancer-specific antibody that provides detailed images of cancer cells in live mice.

Jin-Suck Suh, Jinwoo Cheon and colleagues from Yonsei University, Seoul, produced well-defined nanocrystals of iron oxide (Fe₃O₄) which had superior magnetic properties to conventional iron oxide-based signal enhancers, improving the MR contrast effect.

The crystals were rendered water-soluble and biocompatible by coating with a small organic ligand that also enabled conjugation with herceptin, an antibody with specific attraction towards breast cancer cells. The use of a small ligand, rather than large ligands like dextran employed in conventional probes, conferred greater permeability on the probes within the cells.

This probe was injected into live mice implanted with cancer cells. MR images produced using colour mapping for better signal visualisation revealed that the cancer was targeted within five minutes while the surrounding benign tissue was not targeted.

With a high magnetic field of 9.4 Tesla, the spread of the probe through the cancerous tissue was followed over 12 hour by time-dependent imaging. The complex vascular structures of the tumour were clearly visible, confirming the high permeability of the probes.

Additional in vitro tests confirmed that the probe enhanced the signals of different cancer cell lines. Their applicability was extended further by secondary conjugation with a fluorescent dye-labelled antibody, allowing independent and confirmatory detection of the cancer by optical methods.

’Targeted nanoprobes offer exciting new opportunities in cancer detection and a water-soluble nanocrystal combined with a specific targeted antibody revolutionises our ability to diversify these probes,’ said Nandita deSouza from the Institute of Cancer Research, London, UK. ’The potential of this type of probe is not only to diagnose cancer, but to image very specific tumour characteristics and monitor their response to treatment,’ deSouza told Chemistry World.

These developments will keep MRI at the forefront of cancer detection, say researchers, providing clearer images and safer diagnosis than the radiative techniques of computed tomography (CT or CAT scanning) and X-ray scanning. Steve Down