Novel Fluorescence Imaging Agent May Improve Lung Cancer Surgery

Sunil Singhal, MD, William Maul Measey Professor and chief of Thoracic Surgery at the University of Pennsylvania Perelman School of Medicine, spoke with CancerNetwork® about intraoperative molecular imaging with abenacianine (VGT-309), an investigational, tumor-targeted fluorescent imaging agent that causes tumors to fluoresce during surgery so they are easier for surgeons to see and remove completely. In the phase 2b VISUALIZE trial (NCT06145048), 40 of 89 patients (45%) undergoing lung cancer surgery had at least 1 clinically significant event when the agent was used intraoperatively, which included localization of lesions missed by standard surgical techniques and identification of positive margins.¹

In January 2025, the FDA granted VGT-309 fast track designation in this indication supported by the VISUALIZE findings.² Vergent Bioscience, the agent’s developer, initiated the pivotal phase 3 VISUALIZE 2 trial (NCT07499674) in March 2026, which aims to confirm the agent’s efficacy and safety in lung cancer surgery.³

Singhal discussed the background of the technology, what the clinically significant event rate means in practical terms, equipment compatibility, and why the shift toward minimally invasive surgery has increased the need for intraoperative imaging. He also touched upon what still needs to happen for the technology to become standard practice and where he sees the surgical field heading over the next several years. Overall, he framed intraoperative molecular imaging as an early-stage but rapidly evolving field, with fluorescent tracers poised to play a growing role in cancer surgery as the technology matures.

CancerNetwork: What was the background for the study assessing intraoperative molecular imaging with this agent, VGT-309, during lung cancer surgery?

Singhal: The story goes back almost 2 decades, where many people in the field have been thinking about how to improve cancer surgery. Cancer surgery is one of the best ways to cure people of cancer across the board for any solid cancer: prostate, breast, colon, and lung cancer. The best thing you can do for somebody is take out the cancer. The problem is that in many instances, when you take out the cancer, you leave something behind, whether it’s a positive margin, which means that there’s cancer in the staple line. It could mean that there’s cancer in the lymph nodes that you may have missed. It’s possible that there are extra cancers that you would have missed. The concept of making cancers easier to see is the basis of this technology, and that is injecting a dye into patients that goes to tumors and makes tumors glow or fluoresce. In that method, the surgeons can see the tumors better, know where to cut, make sure they get everything out, and ideally do a better operation for the patient.

This trial showed that 45% of patients had at least 1 clinically significant event. In practical terms, what does that number mean for a patient’s outcome?

What that says is, essentially, if you had 100 patients, in 45 of those 100 patients, using the dye made a meaningful difference in the operation. Whether it was the ability to find something that the surgeon didn’t see, identify the border of the cancer that the surgeon missed, or a situation where the surgeon can’t even find the cancer without the ability to put their fingers or hands in. In that sense, [you] avoid having to make a massive operation or a massive cut or take more tissue than necessary because the dye and the tracer can make the cancer more visible.

Abenacianine works with existing ICG-compatible NIR systems already in most hospitals, unlike agents with compatibility limitations. How much of a barrier has equipment compatibility been to adopting fluorescence-guided surgery more broadly?

These tracers work [by] injecting them into patients. They make tumors fluoresce, but you need a camera that can zoom in to improve the vision and make the cancers brighter. Modern-day cameras are very good at doing that. However, many of these fluorescent agents are specific to certain cameras, and that’s been a big bottleneck for this field. One of the nice aspects of this particular agent is that it works for pretty much any camera that can see the traditional dyes that we already use in the operating room. It avoids situations where you can only use certain cameras with certain tracers, or that you are limited to certain situations or certain hospitals. The advantage of this approach, that this clinical trial addresses, is the ability to image a wide array of patients with a wide array of cameras and avoid a situation where you are bottlenecked to a specific camera.

As lung surgery has shifted toward minimally invasive and sublobar, tissue-sparing resections, surgeons have lost the tactile feedback that open surgery provided. How central is that shift in explaining why intraoperative molecular imaging has become necessary?

Traditionally, before surgery, we’ll [perform] a CT scan and a PET scan, which are traditional imaging approaches. Then, during surgery, we only have our 2 tools: our hands and our eyes. We’re using our eyes to visually locate the tumor, and we’re using the tips of our fingers to feel around and locate the tumor. If you’re having a cancer removed, it’s critical that the surgeon is looking everywhere and using their hands and fingers. Now, we’ve shifted toward minimally invasive surgery, and that’s taken away that tactile option for surgeons. Surgeons depend on their eyes as their only sensory input in determining where to cut, and you’re dependent on the surgeon looking at the films before surgery and making some big, crucial decisions, which could affect the course of that person’s cancer.

The advantage of using these tracers is that, just as minimally invasive surgery and robotics have evolved, tracers meet that need to improve visualization, just as finger palpation and manual palpation started to disappear. As the adoption of minimally invasive surgery continues to increase…the tracers are going to become more important.

A phase 3 trial (NCT07499674) is ongoing, and the technology is already being explored in other diseases like esophageal and breast cancer. What must happen for this to move from clinical trials into a standard part of oncologic surgery?

Well, for any cancer, what needs to be done is clinical trials looking at end points for that specific cancer. For example, for breast cancer, if you’re [treating] something called ductal carcinoma in situ, you want to make sure you get clean margins because it’s very hard to see and feel that type of cancer. If you were a pancreas surgeon, for example, you’d want to make sure that when you cut across the head of the pancreas, you’re taking enough of the pancreas. Part of the process of doing these clinical trials is demonstrating to the medical community that the tracer is providing valuable information. You can imagine a situation where the tracer makes a tumor glow for us, but it doesn’t impact the outcomes of that particular disease. That’s the reason we need to do clinical trials in different subtypes and different types of cancers: to make sure the tracer is adding value everywhere. One of the advantages of [abenacianine] is that it works in many cancer types. It doesn’t depend on a specific receptor; it’s a pathway that’s present in a host of cancers, which allows for a broader range of cancers that it can address.

Beyond this specific agent, how do you see the role of intraoperative molecular imaging evolving over the next 5 to 10 years? Is it heading toward a single pan-cancer agent, or will the field need multiple targeted probes for different tumor biology?

The next decade is hard to predict, but I don’t think there’s ever going to be a single agent. It’s probably not possible. That’s the holy grail of all of cancer biology. It’s never been found, and probably will never be found. Different cancers have different targets, and they have different pathways that are upregulated and downregulated, so I think you will always need multiple tracers. I think there will be tracers that work for several cancer types, and then another tracer that works for other cancer types. Some will overlap and some won’t, and some will be brighter.

There’s a tremendous number of technological advances still coming; dyes are becoming brighter, so they can be better visualized. We’re finding better cameras that can see down to single cancer cells. We’re working on fine-tuning how these tracers interact with robotic machines. There’s a tremendous amount of work going on in the software side, with artificial intelligence, in reading these images. I think the field is changing very rapidly and will continue to evolve over the next decade. We’re just at the tip of the iceberg.

What do you hope others take away from this conversation and your research?

The most important thing is, one, to walk away understanding that this field exists. I think, for a long time, people have understood a little bit about fluorescence-guided surgery or intraoperative molecular imaging, but what this field really is, is the ability to highlight cancers visually. The technology has evolved dramatically to the point where we can be highly sensitive and highly specific. The other key point to take away is that this is a first-of-its-kind tracer for lung cancer, and it’s capable of visualizing a number of tumor types. It doesn’t just see lung cancers in the lung; it can see cancers that metastasize to the lung, for example. There’s a lot of unique features of this tracer, which makes this particular research study exciting.

The results of the study were very promising. We’re moving into a phase 3 clinical trial now, which is the next chapter in the evolution of this technology.

Singhal framed intraoperative molecular imaging as an early-stage but rapidly evolving field, with fluorescent tracers poised to play a growing role in cancer surgery as the technology matures.

References

1. Herrera LJ, Wright GM, Kim JY, Reisenauer JS, Rice DC, Singhal S. Phase II multicenter clinical trial of intraoperative molecular imaging with abenacianine during lung cancer surgery. Ann Surg Oncol. Published online July 26, 2026. doi:10.1245/s10434-026-19951-0
2. Vergent Bioscience receives FDA fast track designation for abenacianine for injection (VGT-309) to help surgeons visualize tumors in the lung during surgery. News release. Vergent Bioscience. January 7, 2025. Accessed August 20, 2026. https://tinyurl.com/bdet8h2u
3. Vergent Bioscience initiates phase 3 VISUALIZE 2 pivotal study of abenacianine (VGT-309) for tumor visualization during lung cancer surgery. News release. Vergent Bioscience. March 17, 2026. Accessed August 20, 2026. https://tinyurl.com/ysbk9yfj