Abenacianine Identifies Occult Lung Tumors, Improves Surgical Margins

According to results from the phase 2b VISUALIZE trial (NCT06145048), published in Annals of Surgical Oncology, intraoperative molecular imaging (IMI) with abenacianine (VGT-309), a cathepsin-targeted, near-infrared (NIR) fluorescent imaging agent, identified at least 1 clinically significant event (CSE) in 40 of 89 patients (44.9%; 95% CI, 34.4%-55.9%) undergoing surgical resection for known or suspected cancer in the lung.¹ The lower bound of the confidence interval ruled out the trial's null hypothesis of a CSE rate ≤10% (P < .0001), meeting the primary efficacy end point. CSEs included localization of a preoperatively identified lesion not found by standard surgical techniques in 33 patients, a synchronous or occult lesion in 3 patients, a margin within 10 mm of the closest staple line in 8 patients, and a cancerous lymph node in 1 patient.

In vivo NIR imaging identified cancerous lesions with a sensitivity of 0.841 (95% CI, 0.757-0.900) and a positive predictive value of 0.750 (95% CI, 0.670-0.816); ex vivo imaging performed slightly better, with a sensitivity of 0.915 (95% CI, 0.845-0.955). No drug-related serious adverse events were reported among the 89 treated patients. The results build on 2 earlier single-center phase 2 trials of abenacianine and support the ongoing phase 3 VISUALIZE 2 trial (NCT07499674), which began enrolling patients in March 2026.

Gavin M. Wright, MBBS, FRACS, PhD, director of surgical oncology at St Vincent's Hospital Melbourne and clinical associate professor in the Department of Surgery at the University of Melbourne, in Melbourne, Australia, and a coauthor of the VISUALIZE trial, spoke with Targeted Oncology™ about the unmet need that prompted the research, the trial's key findings, and what questions remain for the phase 3 study.

Targeted Oncology: What are some of the challenges or unmet needs that prompted this research?

Gavin M. Wright, MBBS, FRACS, PhD: Surgeons have traditionally performed lung cancer surgery through a thoracotomy: a large incision where the ribs are spread apart so the surgeon can put a hand in and feel the whole lung. The problem is, we've become something of a victim of our own success: we invented minimally invasive surgery so we could cause less harm to the patient, and patients recover better with less pain. But now the evidence shows that patients who undergo minimally invasive surgery—video-assisted thoracic surgery or robotic thoracic surgery—actually do better in terms of long-term survival. So, we can't go back to open surgery just because we don't like that we can no longer feel the lung; we have to get over that. Unfortunately, that came at a price: surgeons can no longer feel small tumors in the lung the way we used to and simply cut them out. To make matters worse, a lot of tumors are very small these days because patients have had a CT scan for another reason, or because they were enrolled in a screening program—many states in the US and in Australia have lung cancer screening programs. So, we're finding all these small tumors, and now the surgeon has to find them and remove them without taking too much lung or leaving cancer behind.

We've also learned that not every cancer needs a lobectomy; patients with small, well-located tumors can be cured with a smaller resection. So, surgeons are now in a real bind: we have to do more with less. That's what attracted me to this research—to see whether we could give the surgeon information about where the tumors are, so we can both find them and avoid removing large amounts of lung just hoping the tumor is in there somewhere.

Could you walk us through the study design and what you set out to assess?

We conducted the first VISUALIZE trial, in which patients received a drug that was called VGT-309 at the time and is now known as abenacianine. It's a fluorophore—essentially a dye or chemical that fluoresces, or glows, when hit with a certain frequency of light. The most well-known fluorophore used in medicine is indocyanine green, or ICG, which different specialties use to light up blood vessels, for example. Abenacianine is different because it's a tumor-targeted fluorophore: it won't light up anything except cancer, because it has to bind to the tumor and undergo a chemical reaction before it glows under the light. The idea is to add biological information to the anatomical information we already have. I can see on a CT scan that there's a tumor, but I still have to find that same tumor in the lung.

This study was designed to capture what we call clinically significant events: finding a tumor the surgeon had trouble locating otherwise, finding additional tumors, finding spread to lymph nodes or elsewhere in the lung that we weren't aware of, or finding a metastasis in a different part of the chest. It was a phase 2b study, so every patient received the drug and had the light turned on; we then recorded everything the surgeon found using that near-infrared light.

What did you find, and were any of the results particularly surprising to you?

The most stark finding is that almost half of patients had a clinically significant event. There were 89 patients in the trial, and about 34 of them had tumors found that the surgeon otherwise couldn't find, or had additional tumors identified. There was also a patient who had a lymph node that had previously been biopsied as negative; that node glowed, and when the surgeon removed it, it turned out to contain cancer, which changed that patient's treatment. So, we saw a lot of clinically significant events—over 40% of patients—which tells us this wasn't just showing us a pretty picture of a glowing tumor. It was actually giving surgeons new information that changed what they did in the operating room.

What would you consider the most important takeaway for clinicians?

We’re finding cancers in the lung that are small and hard to find, particularly at the edge or surface of the lung. With lung surgery, a tumor can sit 1 mm below the surface, and the surgeon may not find it unless it's right on the surface, showing up as a scar or an odd spot. With keyhole surgery, the surgeon has no hand inside the chest; you can wave an instrument around and try to feel for something, but you can completely miss a tumor. There have been cases where a whole segment of lung has been removed and the cancer was missed by 2 mm—it's still in the patient, and now they need a second surgery. That's by far the most critical thing this technology addresses.

What research still needs to be done in this area?

We need to show that this gives the surgeon a real edge over current practice. In this trial, every patient received the same treatment, so while the results are encouraging, in medicine we like to compare a new approach against usual care. That's why we're now conducting the phase 3 VISUALIZE-2 trial, a randomized study in which all patients receive the drug, but in 1 of every 10 patients, the surgeon is not permitted to turn on the near-infrared light—that group serves to ensure that the surgeon performs robust usual care in the patient before turning on the light, reflecting what surgeons currently deal with outside of this trial. If we show that the patients who had that advantage of drug actually benefited from it, we'll know abenacianine is better than our current practice.

There are still unanswered questions. Even if this shows that abenacianine improves on current practice, we still need to work out which tumors and which positions in the lung it works best for. We're also now giving patients immunotherapy before surgery, which helps the patient's own immune cells kill the cancer, and it would be wonderful to have a drug that could tell us whether the cancer has been completely killed, partly killed, or not killed at all. That would help surgeons know whether they need to go big or whether they can do a smaller case—maybe they don't need to take that extra piece of lung, or a piece of the aorta, or a piece of bone. That would be the holy grail.

REFERENCE

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