Scorpion Venom Could Help to Detect Brain Tumors: Study

A synthetic version of compound found in scorpion venom could be useful for imaging brain tumors. iStock

Scientists have developed an imaging technique that uses a synthetic version of a compound found in scorpion venom to make brain tumors easier to see, according to the results of an early clinical trial.

Essentially, the technique "lights up" the tumor when viewed through a special camera system, enabling neurosurgeons to get a better picture of the location and extent of malignant growths, which are often difficult to completely remove.

The synthetic compound—a substance known as tozuleristide, or BLZ-100, which is nontoxic and binds to tumor cells—was created by Blaze Bioscience Inc., while the camera system was developed and tested at Cedars-Sinai Medical Center in Los Angeles.

The new approach involves administering BLZ-100 to patients with brain tumors in combination with a fluorescent dye that glows when it is stimulated by a near-infrared laser. The researchers hoped that the boundary between the healthy cells and the tumor itself would become clearer when viewed through a specially developed, high-sensitivity, near-infrared camera.

"With this fluorescence, you see the tumor so much clearer because it lights up like a Christmas tree," Dr. Adam Mamelak, senior investigator of the trial and a pituitary tumor and endoscopic skull base surgery specialist at Cedars-Sinai, said in a statement.

Being able to see the edges of tumors with more clarity would be beneficial to neurosurgeons because it makes the removal of malignant cells easier. When it comes to glioma—a highly lethal form of brain tumor—removal of malignant cells is particularly difficult because they are hard to distinguish from normal brain tissue.

Glioma—which comprise around a third of all brain tumors—do not usually respond to traditional treatments such as chemotherapy or radiation therapy, so effective removal of the tumor may be the patient's only route to survival.

"This technique is aimed at helping surgeons remove tumors while sparing normal tissues," Mamelak told Newsweek. "For surgeons it is often very difficult to determine where a tumor 'ends' and where normal tissue 'begins.' This is especially true in brain tumors that often look very similar to normal brain tissue.

"Removing healthy brain tissue can have significant impact on a person, while leaving residual tumor leads to early tumor recurrence and possible shorter life," he said. "This technique uses fluorescence to help the surgeon differentiate between normal and healthy tissues, thus facilitating more complete tumor removal and less chance of removing healthy normal tissues."

In the clinical trial—which involved 17 adult patients with glioma—the scientists administered varying doses of BLZ-100 before surgery. They found that it made their tumors fluoresce, according to a study published in the journal Neurosurgery.

Using the special camera, surgeons were able to switch between "normal" vision and an enhanced view that showed the tumors fluorescing during surgery.

"The basic technique involves both a drug and a device," Mamelak said. "The drug, tozuleristide, is a combination between a small protein called chlorotoxin, and a fluorescent molecule called Indocyanine green (ICG). Cholorotoxin binds to the cell surface of many malignant tumor cells, and is then internalized. The combination drug is given to a patient and circulates in the blood stream."

"It binds to the tumor and within about two hours, the tumor has a fluorescent tag while normal tissues do not. At surgery, while the surgeon is removing tumor, a special near-infrared camera is used to visualize the tumor," he said. "Therefore, the surgeon is able to see a fluorescence image superimposed on the normal surgical field. The surgeon can then remove areas of fluorescence, resulting in a more complete and accurate tumor removal. Since non-tumor tissues do not fluoresce, the surgeon is also better able to avoid removing those tissues."

Following the operations, the researchers monitored the patients for 30 days, with the initial results indicating that the system was safe to use. However, it is important to note that this trial only involved a small sample size of 17 people, so further research is needed to assess the system's safety before it can be approved for real-world use by the Food and Drug Administration.

"This was a phase I study, so it's really aimed at testing safety and drug dose, with a secondary focus on being able to image tumors," Mamelak said. "The study found that the drug is likely safe, even at doses higher than what is needed to image tumors. There were no significant adverse events. Imaging of tumors could be done any time from two to 36 hours after drug injection, which gives the surgeon a large window of time in which to operate. At higher doses, the majority of the tumors, even low grade ones, showed fluorescence signals."

"However, being a phase I trial, there were several limits," he said. "First and foremost, the camera system used had not been optimized for neurosurgery. This resulted in poor image quality and limited intraoperative imaging overall. In addition, about a third of the patients received low doses of drug, so it is not clear if lack of fluorescence in some of those cases was due to the dose being too low, or a failure [to bind to the] tumor altogether."

To solve this problem, the imaging system was extensively redesigned so that it could be attached directly to a surgical microscope, which significantly improved image quality as well as ergonomics, the researchers say. This setup allows surgeons to visualize the fluorescence throughout the entire surgery, without creating too much interference.

The team say that the next stage of clinical trials assesing the technique has already begun and they are now also looking to refine the camera further so that it can be used seamlessly by surgeons.

Despite the limitations of the study, the researchers say that the technique has shown promise and could help with the imaging of other types of cancers as well. "The ultimate goal is to bring greater precision to the surgical care we provide to our patients," Keith Black, chair of the Department of Neurosurgery at Cedars-Sinai, said in the statement.

This article was updated to include additional comments from Adam Mamelak.