Combining intraoperative imaging with PET scans helps surgeons identify malignant nodules.
Surgeons were able to identify and remove a greater number of cancerous nodules from lung cancer patients when combining intraoperative molecular imaging (IMI) – through the use of a contrast agent that makes tumor cells glow during surgery – with preoperative positron emission tomography (PET) scans. The study from the Abramson Cancer Center at the University of Pennsylvania (ACC) is the first to show how effective the combination of IMI with the tumor–glowing agent can be when combined with traditional PET imaging.

Researchers published their findings in the journal Annals of Surgery.

“Surgically removing tumors still leads to the best outcomes in cancer patients, and this study shows intraoperative molecular imaging can improve the surgeries themselves,” said the study’s lead author Jarrod D. Predina, MD, MS, a post–doctoral research fellow in the Thoracic Surgery Research Laboratory and the ACC’s Center for Precision Surgery. “The more we can improve surgeries, the better the outcomes for these patients will be.”

In order to get live imaging during surgery, Penn researchers used a near–infrared contrast agent called OTL38 that makes tumor cells glow. In past studies, they’ve shown it can detect malignant nodules as small as three millimeters – roughly one–third of the length of a shirt button.

For this study, they combined PET imaging and IMI for 50 patients having surgery to remove lung nodules. All of the patients underwent a pre–operative PET scan within 30 days of their procedure. These scans identified a total of 66 nodules.

During the operation, IMI identified 60 of the 66 previously known nodules, or 91 percent. In addition, doctors used IMI to identify nine additional nodules that were undetected by the PET scan or by traditional intraoperative monitoring. Between PET and IMI, a total of 75 nodules were identified. Researchers found that PET was accurate in determining if nodules were cancerous in 51 of them (68 percent). By comparison, IMI alone was accurate in 68 cases (91 percent). IMI further improved diagnostics in 30 percent of the patients evaluated with this approach. In about 10 percent of patients, IMI helped surgeons find cancer that would have otherwise been missed by standard imaging like CT or PET. “This shows the contrast agent is allowing us to remove more cancer from the patient than we would have with PET imaging alone,” said the study’s senior author Sunil Singhal, MD, the William Maul Measey Associate Professor in Surgical Research and director of the ACC’s Center for Precision Surgery.

Researchers also say this study lays the groundwork for future research involving OTL38. They’re currently evaluating this technology in a formal, multi–center trial that will be the first Phase II study of molecular imaging in the United States. They’re also exploring the effectiveness of additional contrast agents, some of which they expect to be available in clinic within a few months. They will also keep track of these patients to find out if these improved surgeries help patients live longer. These cancers also come back within five years in 25 to 30 percent of cases, so they hope to show these procedures lower that recurrence rate.