Rapid imaging of pulmonary metastasis from colorectal cancer with a red fluorescence probe targeting puromycin-sensitive aminopeptidase and dipeptidyl peptidase IV.

Patients with pulmonary metastasis from primary colorectal carcinoma often undergo sublobar pulmonary metastasectomy. To prevent local cancer recurrence, it is important to ensure an appropriate resection margin. For this purpose, rapid and accurate visualization of cancer lesions by fluorescence imaging would be an effective tool to guide surgeons. Thus, the aim of this study was to find an efficient fluorescence probe for visualizing pulmonary metastases from colorectal cancer. Screening of our aminopeptidase-reactive fluorescence probe library with lysates of metastatic tissues from rectal cancer identified a specifically activated puromycin-sensitive aminopeptidase (PSA)-reactive probe. Based on this finding, we evaluated the utility of our previously reported PSA-reactive red fluorescence probe, QA-2OMeSiR, for fluorescence imaging of pulmonary metastases. QA-2OMeSiR detected pulmonary metastasis from rectal cancer with 83.3% sensitivity and 91.7% specificity (AUC = 0.875). Pulmonary metastasis from colon cancer was detected with 100% sensitivity and 88.9% specificity (AUC = 0.951). Inhibitor experiments and immunohistochemical staining confirmed that the probe targets both PSA and dipeptidyl peptidase IV (DPP-IV). Furthermore, QA-2OMeSiR rapidly visualizes the boundaries of pulmonary metastatic lesions in surgical specimens. These results suggest that QA-2OMeSiR is a promising candidate as a fluorescence probe for rapid intraoperative visualization of pulmonary metastases from colorectal cancer.