The clinical problem the team set out to solve is both common and consequential. Population-based screening programs have dramatically increased the detection of large advanced adenomas, and in the Netherlands alone roughly 4,000 patients each year are diagnosed with polyps larger than two centimeters or early-stage rectal cancer. Treatment for these lesions depends entirely on their biological nature. Polyps containing only low-grade dysplasia, a mild precancerous change, can be removed piecemeal with standard endoscopic techniques available in virtually every hospital. But polyps harboring high-grade dysplasia or early invasive carcinoma demand en-bloc resection, in which the entire lesion is removed in one piece, using sophisticated methods such as endoscopic submucosal dissection or endoscopic intermuscular dissection. These procedures are more complex, more expensive, and restricted to a small cadre of specially trained endoscopists at tertiary centers.

When the distinction is missed, the consequences cascade. If a malignant polyp is understaged and removed piecemeal, pathologists may be unable to assess whether the margins are clear, whether the cancer was completely excised, or whether features indicating lymph node metastasis risk are present. Patients may then require additional major abdominal surgery with substantial complication risks. Even among experts, between 13 and 22 percent of polyps containing high-grade dysplasia or invasive carcinoma go unrecognized, and in community settings that miss rate has been reported to reach a staggering 81 percent. The reverse error is equally costly: overstaging benign polyps triggers unnecessary referrals and operations. Current Dutch guidelines therefore recommend considering en-bloc resection for all rectal polyps larger than two centimeters, yet only about 10 percent of these lesions ultimately prove to contain a malignant component. A large American study found that a quarter of patients undergoing major abdominal surgery for a suspected malignant polyp had benign disease.

The Leiden team’s strategy replaces guesswork with molecular targeting. Their agent, SGM-101, is a chimeric anti-CEA antibody conjugated to a fluorophore called BM-105, which emits light in the near-infrared spectrum. CEA was chosen because earlier work showed it is overexpressed in approximately 75 percent of high-grade dysplasia and early invasive carcinoma cases, while being nearly absent in low-grade dysplasia and normal mucosa in 66 and 98 percent of cases, respectively. When infused intravenously several days before the procedure, the antibody circulates through the body and binds to CEA on malignant cells. A camera system tuned to the fluorophore’s emission wavelength then excites the dye and renders the labeled tissue visible in real time, effectively painting cancer cells in light that the human eye would otherwise never perceive.

In the trial, 22 patients scheduled for en-bloc endoscopic resection of advanced rectal polyps received either 5 or 10 milligrams of SGM-101 via a 30-minute intravenous infusion, three to five days before their procedure. Thirteen of the polyps ultimately proved to contain high-grade dysplasia or invasive carcinoma, while nine contained only low-grade dysplasia, providing both positive and negative test cases. Because standard flexible endoscopes are not yet equipped with fluorescence detection, the researchers used a rigid Quest-Olympus laparoscope introduced transanally through a balloon trocar for in vivo imaging. After resection, specimens were imaged ex vivo on the back table, then sliced into 3-to-5-millimeter bread-loaf sections that were imaged with a Li-Cor PEARL system, allowing direct correlation of fluorescence signals with stained histological slides.

The quantitative results were compelling. On bread-loaf analysis, the median fluorescence intensity rose in step with histological grade, from 0.05 in normal mucosa to 0.14 in low-grade dysplasia and 0.31 in high-grade dysplasia or invasive carcinoma, with all three values significantly different from one another. The primary endpoint, a tumour-to-low-grade-dysplasia ratio, reached a median of 1.7 across the cohort, rising to 2.5 in patients who received the 10-milligram dose compared with 1.3 in the 5-milligram group, a statistically significant difference. The tumour-to-background ratio of 3.7 indicated strong contrast between malignant tissue and normal mucosa. Overall, fluorescence imaging detected high-grade dysplasia and invasive carcinoma with 86 percent sensitivity and 88 percent specificity, remarkable figures for a first-in-context application.

Perhaps most striking was the technology’s ability to correct expert errors. Routine white-light endoscopy, performed by highly experienced gastroenterologists, misclassified the polyp stage in three of the 22 patients. Fluorescence imaging with the clinical Quest system correctly identified the stage in all three cases: two benign polyps wrongly suspected of malignancy showed no fluorescent signal, while one polyp judged benign on white light but harboring high-grade dysplasia lit up precisely at the malignant focus. The imaging did fail in three other cases where conventional assessment was correct, largely due to biological heterogeneity in CEA expression and technical limitations of the rigid scope, which could not visualize three polyps at all because of its restricted angulation.

Those limitations underscore that this remains an early chapter rather than a finished story. The sample was small, with only nine polyps eligible for the primary ratio analysis, and the findings are explicitly hypothesis-generating. The rigid laparoscope restricted inclusion to distal rectal lesions and made positioning awkward. The intravenous agent must be given days before the procedure, whereas an endoscopist would ideally decide during the examination whether fluorescence is needed. CEA expression itself is not uniform across colorectal neoplasia, which likely explains the false negatives. Encouragingly, in the final two patients the team tested a prototype flexible fiber fluorescence endoscope from Olympus ex vivo, and its signals were broadly comparable to the rigid system, supporting a path toward true in vivo fluorescence colonoscopy. The researchers also note that fluorescence ratios showed only a non-significant trend toward predicting invasion depth, a question that will require larger, adequately powered studies.

The broader context makes the advance especially timely. Fluorescence-guided surgery has matured rapidly, with multiple approved agents and commercial camera systems now in operating rooms, but fluorescence-guided endoscopy lags behind, in part because no flexible fluorescence-capable endoscope has yet been commercialized. Other groups have charted parallel routes: a c-Met-targeted tracer once revealed dysplastic colon lesions invisible under white light, a VEGF-A-targeted antibody has assessed treatment response in rectal cancer, and the international CLASSICA trial is exploring the perfusion dye indocyanine green for tissue classification, a tracer spectrally compatible with SGM-101. The Leiden team envisions two realistic implementation pathways: selective use by screening endoscopists facing difficult-to-classify polyps, helping decide between piecemeal removal and referral for en-bloc resection, and use by experts during resection itself to guide the choice between dissection techniques. If larger prospective trials confirm these results, molecular light could transform one of endoscopy’s most persistent uncertainties into a visible answer, sparing countless patients unnecessary surgery while catching dangerous lesions before they escape.

Subject of Research: CEA-targeted near-infrared fluorescence endoscopy for detecting high-grade dysplasia and early invasive rectal cancer

Article Title: CEA-targeted fluorescence endoscopy for the detection of high-grade dysplasia and early invasive rectal cancer: A proof-of-concept trial

Article References: Warmerdam, M. I., Dijkhuis, T. H., Linders, D. J. G., Pesch, C. M. W., Crobach, A. S. L. P., Matoshi, A., Basiliya, K., van den Berg, S. H., Cailler, F., Peeters, K. C. M. J., Holman, F. A., Mieog, J. S. D., Vahrmeijer, A. L., Hilling, D. E., & Boonstra, J. J. (2026). CEA-targeted fluorescence endoscopy for the detection of high-grade dysplasia and early invasive rectal cancer: A proof-of-concept trial. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-026-08155-z

Image Credits: AI Generated

DOI: 10.1007/s00259-026-08155-z

Keywords: fluorescence-guided endoscopy, CEA-targeted imaging, SGM-101, rectal cancer, colorectal polyps, high-grade dysplasia, near-infrared fluorescence, endoscopic submucosal dissection, molecular imaging, clinical trial, cancer detection, Leiden University Medical Center