Fig e LS T colon cancer cell line carcinomatosis model
Fig. 4 e LS174T colon cancer cell line carcinomatosis model. The mouse had multiple tumor implants on the abdominal wall peritoneum and peritoneal surface of abdominal organs. Arrows point to tumors. (Color version of figure is available online.)
which demonstrated a higher expression of Claudin-1 in liver metastases.7 Claudin has also been implicated in promotion of metastases, which is consistent with the higher expression of claudin in patient-derived colon cancer metastases.12
Claudin-1-IRDye800CW was the most effective 48 h after administration, as there was minimal background signal and there were clear tumor margins. When mice were imaged at 24 and 72 h, there was minimal tumor signal compared with surrounding tissue. In orthotopic models, imaging 48 h after administration of Claudin-1-IRDye800CW demonstrated clear tumor margins with no fluorescence of other organs of the gastrointestinal tract. The control mouse that received IR800 dye alone demonstrated fluorescence of the entire mouse and was not localized in any specific tissue due to the nonspecific hematogenous distribution of the dye. When Claudin-1
Fig. 5 e Orthotopic LS174T tumor. (A) Bright-light imaging demonstrates visible local metastases. (B) Fluorescence imaging shows identifiable margins of the tumor and nearby metastases. (Color version of figure is available online.) antibody is conjugated to the NIR dye, the antibody binds to Claudin-1 in the tumor tissue and delivers the dye specifically to the tumor. The other control mouse that was imaged after administration of Claudin-1 alone did not have any fluores-cence signal, which validates that the tumor does not have any interfering autofluorescence.
A recent study was conducted to determine the clinical impact of NIR fluorophoreelabeled λ-Carrageenan on surgical decision-making during resection of head and neck squamous cell carcinoma.13 The authors concluded that antibody-guided fluorescence imaging aided surgical decision-making and improved tumor margin detection. The use of cancer-specific antibodies labeled with NIR fluorophores allows for visuali-zation of tumor margins and tumors otherwise not visible under bright light. Another recent clinical study demonstrated the utility of an anti-CEA antibody tagged to a 700 nm fluo-rophore (SGM-101) for fluorescence-guided surgery of colo-rectal cancer.14 In the present study, we demonstrate that Claudin-1 detects tumor margins in murine models of primary and metastatic colon tumors. Therefore Claudin-1 may be a useful target for use in fluorescence-guided surgery, enhanced imaging, and improved surgical decision-making for colo-rectal cancer. While this application could be applied to all colorectal malignancies, this method would likely be the most clinically relevant in patients with rectal cancer, for improved visualization of tumor burden and for subclinical metastases not visualized with standard imaging techniques. Further studies need to be performed to determine the clinical appli-cation in patients with colorectal cancer.
Studies continue to be conducted to determine the most useful clinical applications for fluorescence imaging.15 Fluo-rescence imaging offers an advantage in debulking cancer operations as altitudinal gradient allows for visualization and detection of subclinical disease at the time of surgery. Fluorescence im-aging also has been demonstrated to improve detection of hepatic metastases derived from colorectal cancers at the time of surgery. In the present study, we have determined that Claudin-1-IRDye800CW detects peritoneal carcinomatosis and metastatic lesions of colon origin in PDOXs, and that Claudin-1-IRDye800CW may be useful for detection and improved visualization of metastases and peritoneal implants at the time of surgery.
One limitation to the use of Claudin-1-IRDye800CW is the significant fluorescent liver signal that was identifiable at all doses. This liver signal would make it difficult to visualize liver metastases with fluorescence imaging. Future studies will be performed with conjugation of Claudin-1 to various NIR dyes to identify a dye that does not have significant liver signal. This conjugate can then be used to study fluorescence imag-ing of liver metastases using Claudin-1 antibody.
Claudin-1-IRDye800CW may be useful for early detection given its implication in tumorigenesis and further studies regarding early detection of polyps may be indicated. Previous studies have utilized a claudin-binding peptide to visualize polyps endoscopically.10 The probe in this study may be useful in the visualization of precancerous lesions during endoscopic evaluation. Further studies should be performed to evaluate the use of Claudin-1-IRDye800CW in early detection of polyps and precancerous lesions. In addition, Claudin-1-IRDye800CW may be useful for fluorescence-guided surgery, as we have r>