A decade of advances in fluorescence-guided cancer surgery

Ten years ago, the Center for Precision Surgery at Penn Medicine was created to develop new intraoperative molecular imaging modalities. Today, the team’s inventions continue to transform cancer surgery. To discuss their successes and the future of intraoperative imaging, Penn Medicine experts Sunil Singhal, MD, Janos Tanyi, MD, PhD, and Edward James Delikatny, PhD, recently joined the Penn Medicine Physician Interviews podcast.

Dr. Singhal is Chief of the Division of Thoracic Surgery and Executive Director of the Center for Precision Surgery. Dr. Tanyi is an Associate Professor of Obstetrics and Gynecology in the Division of Gynecologic Oncology. Dr. Delikatny is a Research Professor of Radiology, and Director of Translational Research at the Center for Precision Surgery.

Improving cancer surgery with intraoperative fluorescence imaging

Prior to the creation of the Center, the three specialists, with colleague neurosurgeon John Y.K. Lee, MD, met on occasion to discuss two common problems in cancer surgery: failure to remove an entire tumor, leaving a positive margin, and difficulty locating and removing all of a cancer's cells. The latter was especially troublesome when many small lesions were spread throughout an area of the body. The resolution to these issues was literally illuminating.

“We were talking about ways to do this operation better, and we identified a possibility to inject patients with contrast agents that fluoresce, or glow,” says Dr. Singhal.

This initial spark led eventually to the Center for Precision Surgery, launched in 2016. The group, which now includes 110 members, has conducted 16 clinical trials to develop a cadre of fluorescent contrast agents. These aides to imaging are injected into patients and taken up by sarcomas, and tumors in the ovary, lung, and brain. In these tissues, they make cancer cells glow so that surgeons can locate the lesions and remove them more completely.

“We have numerous patients who have left the operating room with margins that would’ve been missed by traditional surgery,” Dr. Singhal says. “We’ve also developed ways to identify additional metastases that would’ve been missed." The result, he concludes, is that surgeons at Penn Medicine have been able to really make an impact on patients’ lives.

Leading the way with Cytalux

The creation of intraoperative imaging required new camera designs, new contrast agents, and modified surgical methods, Dr. Delikatny says. From the start, the Center was conceived as a collaborative multidisciplinary endeavor, with participation from surgery, chemistry, radiology, and bioengineering.

Dr. Tanyi was the principal investigator for the initial studies that led to the FDA approval of Cytalux ®, the first molecule for fluorescent imaging in ovarian cancer, a truly groundbreaking accomplishment, Dr. Singhal says, that’s now being used around the country to identify additional lesions in women with ovarian cancer.

In a phase III trial, Dr. Tanyi and his colleagues showed that 33 percent of patients who underwent surgery with Cytalux had additional disease in tissue not originally planned for removal. Research on the approach continues. In 2026, Dr. Tanyi and his colleagues began a new trial to test Cytalux in endometrial carcinoma, and they expect the agent will have many other target applications in the future.

The future of fluorescence-guided cancer surgery

Following the success of Cytalux, the precision surgery team has developed additional tracers for other cancer types. Dr. Delikatny leads that translational work, starting in cells to identify targets that are overexpressed in cancer and ways to make them glow. He then tests the approaches in animal models and veterinary trials before moving to human clinical trials.

Currently, Dr. Delikatny is exploring a variety of new targets, including folate receptors, choline kinase, and signaling phospholipases. “But there are hundreds of other targets we could go after, and we could use multiple dyes to target multiple targets within a single cancer,” he says. Eventually, he hopes to develop a universal tracer that could be used for anyone with any type of cancer, rather than dyes targeted to specific tumor types.

His team is also developing dyes in different wavelength ranges to image deeper tissues with higher resolution. “That’s going to be one of the next big changes in the field, as the dyes develop, as the camera technology develops, and we’re going for deeper, brighter, and sharper images,” Dr. Delikatny says.

As the Center for Precision Surgery continues to lead the field forward, the future is bright for intraoperative molecular imaging. “We’re at the tip of the iceberg, and the Center of Precision Surgery will continue to grow and tackle some of these problems,” Dr. Singhal says.

Referrals and consultations

For a provider-to-provider consultation with Dr. Singhal or Dr. Tanyi, call 877-937-7366, or refer a patient online.