Tumour-specific label pinpoints malignant cells.
Thanks to fluorescent labels that help them to spot cancerous tissue, surgeons have removed ovarian tumour cells that might otherwise have been left behind.
Most malignant ovarian tumours express high numbers of receptors for the molecule folate (also known as vitamin B9), so by attaching the fluorescent molecule fluorescein iso-thiocyanate to folate, researchers created a cancer-cell probe. After injecting this into patients, labelled cells were made to glow white with a special camera and light, allowing surgeons to spot cancerous tissue even when cells were otherwise indistinguishable from their healthy counterparts.
"This provides more accuracy and more certainty for clinicians to remove cancerous cells in real time during surgery," says study leader Vasilis Ntziachristos of the Technical University of Munich in Germany. The results are published today in Nature Medicine1.
Of all the gynaecological cancers — ovarian, vaginal and uterine — ovarian is the greatest killer of women in both the United States and Europe. Removing as much cancerous tissue as possible during surgery is crucial to giving post-operative chemotherapy the best possible chance to kill the remaining cancer cells.
"This advance represents a real paradigm shift in surgical imaging," says Ntziachristos. "Until now we could only rely on the human eye to find carcinogenic tissue, or non-specific dyes that would colour the vascular tissue as well as particular cancer cells. Now we are going after precise molecular signals and not simply physiology."
As a result, in this preliminary study, surgeons were able to remove tumours less than one millimetre in size. In principle, Ntziachristos says, the technique could locate spots of carcinogenic tissue as small as 50 micrometres.
During the past decade, molecular-imaging techniques have been hailed as the "next big thing" Ntziachristos says. Although X-rays, magnetic resonance imaging, computed tomography and ultrasound can all be used to help surgeons determine the size and location of tumours, they cannot differentiate a cancerous cell from a healthy one, limiting the precision of surgical removal. So researchers have turned their attention to optical-imaging techniques and the development of tumour-specific fluorescent probes. This is the first time1 that such tools, originally developed in mice, have been tested in humans.
At this point, says Ntziachristos, this study only constitutes a proof-of-principle. The probes used apply only to ovarian cancer, and one patient's tumour did not fluoresce after being injected with the label. This is to be expected, because folate receptors are only overexpressed by 90–95% of ovarian cancers. To tag 100% of cases might require the use of two different probes.
John Primrose, director of the scientific programme of the Association of Surgeons of Great Britain and Ireland, welcomed the advance, but was doubtful of its wider applications. "This is a significant small step — it's not a paradigm shift, but a significant step," he says. "The problem in its use is that there are not many cancers in which this approach will be helpful."
The next step is to demonstrate that the technique improves outcomes for patients after surgery, and the only way to do that is with a large, randomized clinical trial. "For now we shouldn't celebrate this as an advance — it may not yet be," says Primrose.
van Dam, G. M. et al. Nature Med. http://dx.doi.org/10.1038/nm.2472 (2011).
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Cormier, Z. Glowing cells guide cancer surgeons. Nature (2011). https://doi.org/10.1038/news.2011.544