"The development of biological probes that can guide surgeons, rather than depending only on feel and normal 'white light' to see, can provide tools to navigate the body on a molecular level," said first author Quyen Nguyen, MD, PhD, assistant professor of surgery at the University of California, San Diego School of Medicine.
Surgeons often rely on feel, look and experience to tell if they have removed all of a tumour while sparing healthy tissue. While the patient lies on the operating table under anesthesia, tissue samples are quickly examined by pathologists, and remaining tumour tissue is sometimes missed, meaning further surgery or a greater likelihood of tumour recurrence. Tsien, Nguyen and colleagues used synthetic molecules called activatable cell penetrating peptides (ACPPs) and microscopic nanoparticles to develop probes carrying fluorescent and magnetic tags. These tags make tumours visible to MRI and allow the tumors to "glow" on the operating table. The team wanted to see if the probes could aid surgeons in seeing more of the tumour, particularly the margins.
In a series of studies, working mainly in mice with implanted human tumours, the researchers showed that if tumours had spread to surrounding tissue, the ACCP-nanoparticle probes enabled them to visualize areas of tumours that they wouldn't ordinarily see - either because the tissue was buried beneath other tissue or the tumour simply was difficult to distinguish from normal tissue.
Using a technique called PCR (polymerase chain reaction) to measure tumor DNA, they found that, on average, 90 percent fewer cancer cells remained after surgery to remove tumours in mice using the probe-based molecular guidance compared to surgery without it - a 10-fold reduction. They also found that the fluorescently labelled probes hit their mark 93 percent of the time, allowing the researchers to "see" left over tumour tissue.
According to the scientists, only a single injection of the nanoparticle-based probe containing the fluorescent and magnetic tags was needed in order to use MRI to examine the entire mouse model for tumours before and after surgery, in addition to the real-time guidance in surgery.
Nguyen said that in the future, additional tags may be added, and eventually, a cocktail of personalised probes may be designed for individual types of cancers. If the nanoparticle-based probes are successful in finding tumour cells in humans, the researchers envision using them eventually to deliver chemotherapy drugs to finish off the remaining cancer.
Tsien and Nguyen see many advantages to molecularly guided cancer surgery. Probes can be useful in staging cancer, particularly in prostate cancer, and can be used in a variety of tumour types. In addition, such biological probes can be used in laparoscopic and robotic surgery, where surgeons cannot feel the tumour, and rely much more on sight. If surgeons can completely remove a cancer, it may mean a patient could be cured quickly, and at relatively low cost when compared to long-term chemotherapy.