Abstract
Early detection of esophageal squamous cell carcinoma (ESCC) is an important prognosticator, but is difficult to achieve by conventional endoscopy. Conventional lugol chromoendoscopy and equipment-based image-enhanced endoscopy, such as narrow-band imaging (NBI), have various practical limitations. Since fluorescence-based visualization is considered a promising approach, we aimed to develop an activatable fluorescence probe to visualize ESCCs. First, based on the fact that various aminopeptidase activities are elevated in cancer, we screened freshly resected specimens from patients with a series of aminopeptidase-activatable fluorescence probes. The results indicated that dipeptidylpeptidase IV (DPP-IV) is specifically activated in ESCCs, and would be a suitable molecular target for detection of esophageal cancer. Therefore, we designed, synthesized and characterized a series of DPP-IV-activatable fluorescence probes. When the selected probe was topically sprayed onto endoscopic submucosal dissection (ESD) or surgical specimens, tumors were visualized within 5 min, and when the probe was sprayed on biopsy samples, the sensitivity, specificity and accuracy reached 96.9%, 85.7% and 90.5%. We believe that DPP-IV-targeted activatable fluorescence probes are practically translatable as convenient tools for clinical application to enable rapid and accurate diagnosis of early esophageal cancer during endoscopic or surgical procedures.
Highlights
In order to detect early-stage esophageal squamous cell carcinomas (ESCCs) in the absence of signs or symptoms, endoscopic screening of the esophagus is usually conducted with the aid of lugol chromoendoscopy or image-enhanced endoscopy, such as narrow-band imaging (NBI)[6,7], since early-stage ESCCs are difficult to see in conventional endoscopy owing to the poor visual contrast between cancer and normal tissues under white light
We found that this probe is unsuitable for detecting ESCCs in clinical specimens, and we considered that a target other than GGT would be required for fluorescence-guided detection of esophageal cancers
In order to find an aminopeptidase activity that is specific for ESCCs, and to ensure that the findings would be directly translatable to clinical application, we carried out screening using fresh biopsy samples taken from cancer-positive and negative sites during preoperative upper gastrointestinal endoscopic examination of patients
Summary
In order to detect early-stage ESCCs in the absence of signs or symptoms, endoscopic screening of the esophagus is usually conducted with the aid of lugol chromoendoscopy or image-enhanced endoscopy, such as narrow-band imaging (NBI)[6,7], since early-stage ESCCs are difficult to see in conventional endoscopy owing to the poor visual contrast between cancer and normal tissues under white light. We recently confirmed the suitability of this probe, γ-glutamyl hydroxymethylrhodamine green (gGlu-HMRG), for detecting human breast cancer in resected tissue from patients[16]. We firstly employed a screening strategy to identify a suitable target aminopeptidase for visualizing esophageal cancer, using freshly resected specimens from patients and a series of aminopeptidase-activatable fluorescence probes. We confirmed that the selected probe could rapidly visualize tumors in freshly resected endoscopic submucosal dissection (ESD) specimens and surgical specimens with high sensitivity, specificity and accuracy
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