Colorectal cancer (CRC) is one of the most common and deadly forms of cancer. Surgery is often the primary treatment method, with complete surgical tumor resection associated with better overall survival and lower recurrence rates.
However, complete resection remains a challenge in many patients, particularly in advanced or recurrent cancer cases. Positive resection margins are standard, and accurate differentiation between malignant and benign tissue during surgery can be difficult.
To address this challenge, researchers are exploring using near-infrared (NIR) fluorescence imaging technology, which involves using targeted probes and a fluorescence imaging system to identify specific molecular targets on tumor tissue.
While conventional fluorescence-guided surgery focuses on the first near-infrared window (NIR-I, 700-900 nm), which has limited tissue penetration depth, the second near-infrared window (NIR-II, 1000-1700 nm) allows for deeper tissue penetration and higher resolution.
In a recent study published in eBioMedicine, researchers conjugated an anti-CEACAM5 nanobody with the near-infrared fluorescent dye IRDye800CW to create a targeted NIR-II probe. CEACAM5 is overexpressed in 90% of CRC, making it an ideal imaging target. The study aimed to explore the potential value of NIR-II fluorescence in intraoperative navigation of colorectal cancer.
While there are already many NIR-II fluorescent probes with excellent imaging performance, the unknown immunogenicity of current fluorescent dyes limits their clinical conversion potential. However, this study shows promise in improving the precision of CRC surgery. It could potentially lead to more effective treatment options for patients with this deadly disease.
T surgery is still the primary method for treating colorectal cancer (CRC). Still, complete removal of the tumor remains difficult. To address this challenge, researchers are exploring a new technique called a near-infrared window (NIR-II) fluorescent molecular imaging, which can potentially be used for tumor surgical navigation.
Researchers were able to build a NIR-II probe specific for colorectal cancer termed 2D5-IRDye800CW by combining the anti-CEACAM5 nanobody 2D5 with the fluorescent dye IRDye800CW.
The 2D5-IRDye800CW I demonstrated excellent NIR-II (1000 nm-1600 nm) imaging capabilities in both in vitro and in vivo studies, with higher resolution and less tissue scattering; a higher tumor binding ratio (TBR) was observed for NIR-II tumor imaging in vivo than for NIR-I imaging, 2.55 0.38 (NIR-II) versus 1.94 0.20 (NIR-I) (NIR-I), The binding of these targeted probes by high molecular weight monoclonal antibodies with prolonged half-lives in -DOTA-labetuzumab-IRDye800CW,10,43,44 causes non-specific background signals, peak fluorescence buildup around the tumor, and a delay in probe clearance.
To arrange surgery for the best imaging time, specific probes must be inserted for two to four days, and often even six days, ahead of time. Several medical settings, including regular endoscopy, do not allow for this. Because CEA is the leading biomarker for detecting colorectal cancer in vivo, researchers used a low-molecular-weight anti-CEACAM5 nanobody to produce imaging probes with good stability, affinity, metabolism, and permeability.
It is preferable to obtain diagnostic imaging findings on the same day. When 2D5-IRDye800CW is injected into the tail vein, tumor cells that overexpress CEACAM5 may be connected (15-30 min).
Tumors beneath the skin generate a more excellent fluorescence signal than the surrounding skin (TBR = 1.7), suggesting high permeability and quick imaging. Additionally, fluorescent signal intensity in cancer tissue is still visible 48 hours after injection (TBR = 2.1), and the 2-48 hour imaging window allows for some flexibility in timing probe injections and surgical operations. Topical dispersion is the most practical approach for dispersing FGS-targeted drugs due to its quick imaging and low molecular weight.
Despite their outstanding imaging potential, NIR-II fluorophores, such as semiconducting inorganic nanomaterials and newly discovered small-molecule organic dyes, confront technological and regulatory barriers that prevent them from entering commercial usage. This study does not compare recurrence and survival rates following tumor excision guided by white light against NIR-II.
Clinical laparoscopy is often used in colorectal cancer surgery. However, all orthotopic mice models need open abdominal cavity imaging. Open abdominal visual field imaging is presently the standard for NIR-II intraoperative navigation. This study looked into CRC NIR-II imaging applications. The use of fluorescence endoscopy for intraoperative NIR-II navigation will hasten clinical deployment.
