Lighting up for life - successful use of fluorescence dye in the fight against cancer under construction

Prof. Gooitzen M van Dam, a leading surgeon at the Department of Surgery, Division of Surgical Oncology at RUG, and his team performed the first ever fluorescence-guided surgery on a patient with ovarian cancer. This surgery demonstrated the feasibility and potential of the innovative flourescence-imaging technique for removing cancerous cells through surgery. The results, published recently in the prestigious journal Nature Medicine reveal that the new technique is a huge step forward in providing surgeons with an effective tool in their fight against cancer.

The big picture

Currently, the most widely used methods for imaging cancerous tissue employ radiological techniques like X-ray, CT scan, MRI and ultrasound imaging. Useful as they are, such techniques provide relatively coarse image resolution and no real-time feedback on the location of cancerous tissues during excision surgeries. Such limitations force surgeons to rely mainly on visual and tactile examination. As a result, research into innovative optical imaging methods has picked up speed in the last decade. Attaching fluorescent dye agents to molecules or proteins that are "consumed" by cancerous cells is one such promising technique that has been successfully tested in mice. Once inside the cancerous cells, the fluorescent agents light them up and reveal their precise location. Given that most cancer treatments involve a combination of surgical tissue excision and post-surgical chemotherapy, knowing the precise location of cancerous cells in real-time as they are being surgically removed is of paramount importance for the success of the treatment and ultimately will prove decisive for the patient's life.

A new standard in cancer surgery

An international collaborative effort to develop a high-resolution, high-sensitivity fluorescence imaging tool has culminated in a ready-to-use system that can aid surgeons in the detection and removal of malignant ovarian cancer tissue in humans. The new technology was tested during a surgery performed by a highly-skilled team at University Medical Centre Groningen, with the supervision of prof. Gooitzen M van Dam. This was the first successful surgery performed on humans using fluorescent agents as a way to image the cancerous tissue. "I think this technology will revolutionize surgical vision. I foresee it becoming a new standard in cancer surgery in a very short time." - said Prof. Gooitzen M van Dam.

Why ovarion cancer?

Studies have shown that of all the gynaecological cancers, ovarian cancer is the number one killer in both Europe and the United States. Diagnosis at an early stage is very difficult because the initial development of ovarian cancer is slow and the symptoms are too general to effectively pinpoint the cause. Furthermore, spotting ovarian cancer tissue during surgery using conventional techniques, namely visual and tactile examination, is often problematic. This leads to poor removal of the cancerous cells and more often than not, the remaining cancer tissue cannot be completely eradicated by post-surgical chemotherapy.

Prof. Philip Low from Purdue University who is a co-author of the paper published in Nature Medicine discovered that ovarian cancer cells exhibit strong receptive behaviour towards folic acidin 90-95% of ovarian cancer patients. This discovery provided an opportunity for the development of an imaging marker, consisting of a fluorescent dye agent, attached to a folate molecule. Folate receptors are not present in healthy tissue, and the fluorescent dye lights up the cancerous cells in stark contrast with healthy tissue. Such markers have already been developed for imaging tumours in mice, but have never been tested in humans.  

First results

According to Prof. Low the new fluorescence-imaging technique has a resolution as high as one tenth of a millimeter. " ...this technique allowed surgeons to spot a tumour 30 times smaller than the smallest they could detect using standard techniques" he said. Indeed, all the surgeons who used the new fluorescent-guided imaging system found on an average, 34 tumour deposits compared to 7 when they used the conventional techniques- an improvement of 485%! Furthermore, according to prof. Gooitzen M van Dam, the imaging system fits well with existing surgical practices. "This system is very easy to use and fits seamlessly in the way surgeons do open and laparoscopic surgery, which is the direction most surgeries are headed in the future," he added (1). What's more, the new imaging technique is safe and cost effective since folate based markers are non toxic and inexpensive.

The future

After the initial euphoria around the first in-human fluorescent-guided ovarian cancer surgery subsided, prof. Gooitzen M van Dam and his colleagues admit they have a lot more work ahead of them. Ovarian cancer tissues are one of the few that exhibit very strong inclination towards folic acid absorption. This inclination progressively goes down in case of lung, kidney, breast and colon cancer. New tumourspecific fluorescent markers need to be developed in order to achieve similar results in patients with these types of cancer. As for ovarian cancer, the next step is to demonstrate the overall improvement in the treatment of patients. This can only be done with a lengthy and large randomized clinical trial. Nevertheless, the medical community in particular, and humanity as a whole have a reason to celebrate an important next step in our fight against cancer. We, at RUG are proud that our academic and research staff is marching on the frontline.

References:

1. Purdue technology used in first fluorescence-guided ovarian cancer surgery , Purdue University News Service, Sept 2011