Penn’s Fluorescent Dye Used During Surgery Identifies Pituitary Adenomas, a Cause of Cushing’s

Researchers at the Perelman School of Medicine at the University of Pennsylvania have successfully used a fluorescent dye to identify pituitary adenoma tissue during brain surgery.

The study, “Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging,” was published in the Journal of Neurosurgery.

“Pituitary adenomas are rarely cancerous, but they can cause other serious problems for patients by pushing up against parts of their brain, which can lead to Cushing’s disease, gigantism, blindness, and death,” study first author John Y.K. Lee said in a press release. “The study shows that this novel, targeted, near-infrared fluorescent dye technique is safe, and we believe this technique will improve surgery.”

Pituitary adenomas are the third most common brain tumor. Surgery is the primary approach for treating these tumors, but the extent of tumor resection is based only on the visual and tactile perception of surgeons.

In this new study, authors based their approach on previous clinical trials suggesting that a molecular imaging agent developed at Penn’s Center for Precision Surgery could improve procedures to remove tumors.

The molecule, known as OTL38, is a folate analog linked to a fluorescent dye that glows when a near fluorescent light is used.

Pituitary tumors produce up to 20 times more folate receptors than normal pituitary cells. This suggested that a folate analog like OTL38 could be specific to pituitary adenoma cells. And being linked to a fluorescent dye, the molecule could work as a real-time imaging agent for identifying the tumor tissue during surgery.

The team tested the approach in 15 patients. They used an endoscope equipped with a camera to illuminate the pituitary adenomas, inserted through the nasal cavity. The technique was safe and effective at illuminating the tumors, they found.

Using MRI scans, the researchers measured the amount of tumor cells that remained after surgery, revealing that OTL38 improved the effectiveness of the procedure compared to conventional approaches.

“This study heralds a new era in personalized tumor surgery. Surgeons are now able to see molecular characteristics of patients’ tumors; not just light absorption or reflectance,” said Lee, who is also an associate professor of neurosurgery in the Perelman School of Medicine and co-director of the Center for Precision Surgery. “In real time in the operating room, we are seeing the unique cell surface properties of the tumor and not just color. This is the start of a revolution.”

Now, researchers are exploring new contrast agents to assess their feasibility and efficacy during surgery.

“This is the beginning of a whole wave of new dyes coming out that may improve surgeries using the fluorescent dye technique,” Lee said. “And we’re leading the charge here at Penn.”