Surgery is the cornerstone of curative-intent treatment of patients with solid cancers. Complete removal of the tumor is pivotal for prolonged survival outcomes. Unfortunately, tumor-positive resection margins occur in 8-70% of cases depending on cancer type. Evidently, there is an unmet need for a technique to improve tumor detection and margin assessment in real-time during surgery.

Intraoperative tumor-targeted near-infrared (NIR) fluorescence imaging enables visualization of (residual) tumor rapidly, non-invasively and in real-time with high spatial accuracy. The development and clinical translation of newly designed tumor-targeted NIR imaging agents is essential, because none of the available imaging agents can be used in all tumor types due to variable protein expression profiles. Development and clinical translation of imaging agents is a costly and time-consuming process, as it comprises many different stages and requires strict regulatory assessments to ensure patient safety and agent efficacy.

Most solid cancers are treated by surgical resections to reduce the burden of disease. Surgeons often face the challenge of detecting small areas of residual neoplasm after resection or finding small primary tumors for the initial resection. Intraoperative molecular imaging (IMI) is an emerging technology with the potential to dramatically improve cancer surgery operations by allowing surgeons to better visualize areas of neoplasm using fluorescence imaging. Over the last two years, two molecular optical contrast agents received U.S. Food and Drug Administration approval, and several more drugs are now on the horizon. Thus a conference was organized at the University of Pennsylvania to bring together oncologic surgeons from different specialties to discuss the current clinical status of IMI trials with a specific focus on phase 2 and phase 3 studies. In addition, phase 1 and experimental trials were also discussed briefly, to highlight other novel techniques. Our review summarizes the discussions from the conference and delves into the types of cancers discussed, different contrast agents in human trials, and the clinical value being studied.