Metastatic detection: MRI nano-tracking

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  • Published: Oct 1, 2012
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: Metastatic detection: MRI nano-tracking

Glowing cancer report

Scavening for integrins with nanochains to beat metastases. Credit: American Chemical Society/Karathanasis  et al  

Fluorescence molecular tomography and magnetic resonance imaging can exploit new nanotechnology to facilitate the identification of metastatic breast cancer cells before they grow into untreatable tumours. The work might eventually reduce the mortality rates in this disease.

Cancer cells can break away from a primary tumour, spread through the lymph system and bloodstream and implant new sites of malignancy elsewhere in the body. It is this process of metastasis that increases mortality in cancer. Researchers at Case Western Reserve University have now developed a nanotech system for locating metastases in a mouse model of breast cancer much earlier in the disease than was possible with current methods. The work involves the use of fluorescence molecular tomography and MRI to locate the metastases, which could ultimately allow a life-saving diagnosis in humans to be made early enough after breast cancer diagnosis to allow effective treatment to be given.

An interdisciplinary team of researchers from five disciplines have linked together to build nanochains that can home in on metastatic cells before they grow into new cancerous tissues. The work could one day guide surgeons right to the site of relocated cancer cells where they can ablate the rogue cells or inject cytotoxic drugs directly.

"Micrometastases cannot be seen with the naked eye, but you have to catch them at this stage – see the exact spots they're located and see them all," explains senior author of the research Efstathios Karathanasis. "Even if you miss only one, you prolong survival, but one metastasis can still kill."

Until now, standard tumour detection technologies fail to reveal the presence of metastatic cancer cells at this stage until they are putatively beyond treatment. The new approach offers hope that even metastatic cancer might be treated with much greater success rates than are possible with current approaches.

The team explains that once a breast cancer cell has detached from an actual breast cancer and entered the bloodstream, it can reach the liver, spleen or lungs and once there begins overexpressing surface proteins, integrins, which allow it to bind to the interior wall of a blood vessel. "We target integrins," Karathanasis explains. "Normal blood vessel walls don't present integrins towards the blood site unless cancer cells attach there." To home in on the cancer marker, the researchers tailored nanoparticles to connect one to another rather than being the conventional spherical shape. These nanochains skirt along the inner wall of blood vessels rather than going with the flow. The chains can bond to integrins at a rate ten times higher than spherical nanoparticles and allow the metastatic cells to be imaged view their inbuilt fluorescent markers. Iron oxide links in the nanochains make them visible to MRI.

Tests in a mouse model of aggressive breast cancer, the kind that rapidly metastasises, as it does in humans, have shown that these rogue cells can be detected within an hour using the nanochains and those two techniques. Additional magnified imaging revealed that the metastatic cancer cells were found mostly in the blood vessel walls and hadn't implanted into organ tissue. It is at this stage that one would assume greater treatment success might be wrought.

'static success with nanochains

"Once metastatic cells move into the tissue, develop their own microenvironment, and grow into a 1-centimetre lesion, it typically indicates a late stage of metastatic disease which has an unfavourable outcome," Karathanasis adds, it's usually terminal, in other words.

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Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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